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Last Name
Institution

Hong-Gang Wang

TitleProfessor
InstitutionCollege of Medicine
DepartmentPediatrics
Address500 University Drive Hershey PA 17033
Mailbox: CH74
Phone717-531-4574

 Overview 
 overview
PREFERRED TITLE/ROLE:

Lois High Berstler Professor, Pediatrics and Pharmacology
Director, Pediatric Molecular Oncology Program

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Pharmacology, Penn State Hershey Children’s Hospital, Penn State Hershey Cancer Institute, The Huck Institutes of the Life Sciences

GRADUATE PROGRAM AFFILIATIONS:

Cell and Molecular Biology, Pharmacology, Biomedical Sciences: Translation Therapeutics Option, Integrative Biosciences: Molecular Medicine

EDUCATION:

B.S., University of Tsukuba, 1987
Ph.D., University of Tsukuba, 1992
Postdoctoral Training, Burnham Institute, 1993-1998

NARRATIVE:

Research in this laboratory is concerned with understanding the interplay of autophagy (self-eating) and apoptosis (self-killing) in the context of tumorigenesis and drug resistance. In addition, targeting of these two closely related but distinct self-destructive processes for anticancer drug discovery and development is another major interest of our research group. We discovered a novel tumor suppressor, Bif-1, that activates not only apoptosis but also autophagy. Bif-1 is involved in the conformational activation of Bax, a key pro-apoptotic Bcl-2 family member, at the mitochondria during apoptosis. Bif-1 interacts with BECN1 through UVRAG and regulates autophagosome formation and Atg9 trafficking during nutrient starvation. The expression of Bif-1 is decreased in various human cancers, and the deletion of Bif-1 promotes tumor development in mouse models. Our work on AMPK association with ULK1 was among the first to link a cellular energy sensor to the core autophagy machinery. We found that AMPK directly binds to ULK1, and this interaction is required for ULK1-mediated autophagy. Our studies unveiled a dual-armed intracellular death-inducing signaling complex (iDISC) that assembles on the autophagosomal membrane to mediate caspase-8 activation and initiation of the apoptotic cascade. This work has significant translational impact in identifying a mechanism by which the survival process of autophagy can be switched towards cell death to enhance the therapeutic efficacy of anticancer drugs. In addition, our group has identified the natural product marinopyrrole A (maritoclax) and its derivatives as a novel class of Mcl-1 inhibitors that antagonize Mcl-1 and overcome multidrug resistance in hematological malignancies by targeting Mcl-1 for proteasomal degradation. This unique mechanism of action is in sharp contrast to canonical BH3 mimetics that exert their inhibitory function through disruption of pro- and anti-apoptotic Bcl-2 family protein complexes. The ultimate goal of our research is to translate basic science discoveries to the development of new approaches for the treatment and prevention of cancer.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Niu G, Zhang H, Liu D, Chen L, Belani C, Wang HG, Cheng H. Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex. J Biol Chem. 2015 Jul 17; 290(29):18102-10.
    View in: PubMed
  2. Varadarajan S, Poornima P, Milani M, Gowda K, Amin S, Wang HG, Cohen GM. Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner. Oncotarget. 2015 May 20; 6(14):12668-81.
    View in: PubMed
  3. Wang DB, Kinoshita Y, Kinoshita C, Uo T, Sopher BL, Cudaback E, Keene CD, Bilousova T, Gylys K, Case A, Jayadev S, Wang HG, Garden GA, Morrison RS. Loss of endophilin-B1 exacerbates Alzheimer's disease pathology. Brain. 2015 Jul; 138(Pt 7):2005-19.
    View in: PubMed
  4. Hsu P, Liu X, Zhang J, Wang HG, Ye JM, Shi Y. Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. Autophagy. 2015 Apr 3; 11(4):643-52.
    View in: PubMed
  5. Dick TE, Hengst JA, Fox TE, Colledge AL, Kale VP, Sung SS, Sharma A, Amin S, Loughran TP, Kester M, Wang HG, Yun JK. The Apoptotic Mechanism of Action of the Sphingosine Kinase 1 Selective Inhibitor SKI-178 in Human Acute Myeloid Leukemia Cell Lines. J Pharmacol Exp Ther. 2015 Mar; 352(3):494-508.
    View in: PubMed
  6. Doi K, Gowda K, Liu Q, Lin JM, Sung SS, Dower C, Claxton D, Loughran TP, Amin S, Wang HG. Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells. Cancer Biol Ther. 2014 Dec 2; 15(12):1688-99.
    View in: PubMed
  7. Chen SJ, Hoffman NE, Shanmughapriya S, Bao L, Keefer K, Conrad K, Merali S, Takahashi Y, Abraham T, Hirschler-Laszkiewicz I, Wang J, Zhang XQ, Song J, Barrero C, Shi Y, Kawasawa YI, Bayerl M, Sun T, Barbour M, Wang HG, Madesh M, Cheung JY, Miller BA. A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth through Hypoxia-inducible Factor (HIF)-1/2a. J Biol Chem. 2014 Dec 26; 289(52):36284-302.
    View in: PubMed
  8. Muppidi A, Doi K, Ramil CP, Wang HG, Lin Q. Synthesis of cell-permeable stapled BH3 peptide-based Mcl-1 inhibitors containing simple aryl and vinylaryl cross-linkers. Tetrahedron. 2014 Oct 21; 70(42):7740-7745.
    View in: PubMed
  9. Sun X, Hasanali ZS, Chen A, Zhang D, Liu X, Wang HG, Feith DJ, Loughran TP, Xu K. Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia. Br J Haematol. 2015 Feb; 168(3):371-83.
    View in: PubMed
  10. Doi K, Liu Q, Gowda K, Barth BM, Claxton D, Amin S, Loughran TP, Wang HG. Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression. Cancer Biol Ther. 2014 Aug; 15(8):1077-86.
    View in: PubMed
  11. Wang DB, Uo T, Kinoshita C, Sopher BL, Lee RJ, Murphy SP, Kinoshita Y, Garden GA, Wang HG, Morrison RS. Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. J Neurosci. 2014 Feb 12; 34(7):2674-83.
    View in: PubMed
  12. Muppidi A, Doi K, Edwardraja S, Pulavarti SV, Szyperski T, Wang HG, Lin Q. Targeted delivery of ubiquitin-conjugated BH3 peptide-based Mcl-1 inhibitors into cancer cells. Bioconjug Chem. 2014 Feb 19; 25(2):424-32.
    View in: PubMed
  13. Ren T, Takahashi Y, Liu X, Loughran TP, Sun SC, Wang HG, Cheng H. HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains. Oncogene. 2015 Jan 15; 34(3):334-45.
    View in: PubMed
  14. Ryland LK, Doshi UA, Shanmugavelandy SS, Fox TE, Aliaga C, Broeg K, Baab KT, Young M, Khan O, Haakenson JK, Jarbadan NR, Liao J, Wang HG, Feith DJ, Loughran TP, Liu X, Kester M. C6-ceramide nanoliposomes target the Warburg effect in chronic lymphocytic leukemia. PLoS One. 2013; 8(12):e84648.
    View in: PubMed
  15. Pandey MK, Gowda K, Doi K, Sharma AK, Wang HG, Amin S. Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells. PLoS One. 2013; 8(11):e78570.
    View in: PubMed
  16. He S, Ni D, Ma B, Lee JH, Zhang T, Ghozalli I, Pirooz SD, Zhao Z, Bharatham N, Li B, Oh S, Lee WH, Takahashi Y, Wang HG, Minassian A, Feng P, Deretic V, Pepperkok R, Tagaya M, Yoon HS, Liang C. PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. Nat Cell Biol. 2013 Oct; 15(10):1206-19.
    View in: PubMed
  17. Takahashi Y, Young MM, Serfass JM, Hori T, Wang HG. Sh3glb1/Bif-1 and mitophagy: acquisition of apoptosis resistance during Myc-driven lymphomagenesis. Autophagy. 2013 Jul; 9(7):1107-9.
    View in: PubMed
  18. Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK, Wang HG, Bhalla KN. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A. 2013 Apr 23; 110(17):6841-6.
    View in: PubMed
  19. Takahashi Y, Hori T, Cooper TK, Liao J, Desai N, Serfass JM, Young MM, Park S, Izu Y, Wang HG. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood. 2013 Feb 28; 121(9):1622-32.
    View in: PubMed
  20. Takahashi Y, Young MM, Wang HG. SNAPping off Golgi membranes for autophagosome formation. Cell Cycle. 2013 Jan 1; 12(1):15-6.
    View in: PubMed
  21. Young MM, Kester M, Wang HG. Sphingolipids: regulators of crosstalk between apoptosis and autophagy. J Lipid Res. 2013 Jan; 54(1):5-19.
    View in: PubMed
  22. Liu Q, Wang HG. Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors. Commun Integr Biol. 2012 Nov 1; 5(6):557-65.
    View in: PubMed
  23. Muppidi A, Doi K, Edwardraja S, Drake EJ, Gulick AM, Wang HG, Lin Q. Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors. J Am Chem Soc. 2012 Sep 12; 134(36):14734-7.
    View in: PubMed
  24. Ren T, Dong W, Takahashi Y, Xiang D, Yuan Y, Liu X, Loughran TP, Sun SC, Wang HG, Cheng H. HTLV-2 Tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy. J Biol Chem. 2012 Oct 5; 287(41):34683-93.
    View in: PubMed
  25. Runkle KB, Meyerkord CL, Desai NV, Takahashi Y, Wang HG. Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation. Cancer Biol Ther. 2012 Aug; 13(10):956-66.
    View in: PubMed
  26. Kim YB, Balasis ME, Doi K, Berndt N, DuBoulay C, Hu CC, Guida W, Wang HG, Sebti SM, Del Valle JR. Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction. Bioorg Med Chem Lett. 2012 Sep 15; 22(18):5961-5.
    View in: PubMed
  27. Ding W, Dang H, You H, Steinway S, Takahashi Y, Wang HG, Liao J, Stiles B, Albert R, Rountree CB. miR-200b restoration and DNA methyltransferase inhibitor block lung metastasis of mesenchymal-phenotype hepatocellular carcinoma. Oncogenesis. 2012; 1:e15.
    View in: PubMed
  28. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG. Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem. 2012 Apr 6; 287(15):12455-68.
    View in: PubMed
  29. Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran TP, Sebti S, Wang HG. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23; 287(13):10224-35.
    View in: PubMed
  30. Watters RJ, Wang HG, Sung SS, Loughran TP, Liu X. Targeting sphingosine-1-phosphate receptors in cancer. Anticancer Agents Med Chem. 2011 Nov; 11(9):810-7.
    View in: PubMed
  31. Zhang Y, Cheng Y, Zhang L, Ren X, Huber-Keener KJ, Lee S, Yun J, Wang HG, Yang JM. Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression. Biochem Biophys Res Commun. 2011 Oct 14; 414(1):129-34.
    View in: PubMed
  32. Liao A, Broeg K, Fox T, Tan SF, Watters R, Shah MV, Zhang LQ, Li Y, Ryland L, Yang J, Aliaga C, Dewey A, Rogers A, Loughran K, Hirsch L, Jarbadan NR, Baab KT, Liao J, Wang HG, Kester M, Desai D, Amin S, Loughran TP, Liu X. Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia. Blood. 2011 Sep 8; 118(10):2793-800.
    View in: PubMed
  33. Kulkarni SS, Hu X, Doi K, Wang HG, Manetsch R. Screening of protein-protein interaction modulators via sulfo-click kinetic target-guided synthesis. ACS Chem Biol. 2011 Jul 15; 6(7):724-32.
    View in: PubMed
  34. Coppola D, Helm J, Ghayouri M, Malafa MP, Wang HG. Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. Pancreas. 2011 Apr; 40(3):433-7.
    View in: PubMed
  35. Takahashi Y, Meyerkord CL, Hori T, Runkle K, Fox TE, Kester M, Loughran TP, Wang HG. Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy. Autophagy. 2011 Jan; 7(1):61-73.
    View in: PubMed
  36. Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, Rodriguez JM, Becerril J, Berndt N, Hamilton AD, Wang HG, Sebti SM. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem. 2011 Mar 18; 286(11):9382-92.
    View in: PubMed
  37. Lee JW, Park S, Takahashi Y, Wang HG. The association of AMPK with ULK1 regulates autophagy. PLoS One. 2010; 5(11):e15394.
    View in: PubMed
  38. Yang J, Takahashi Y, Cheng E, Liu J, Terranova PF, Zhao B, Thrasher JB, Wang HG, Li B. GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death. J Cell Sci. 2010 Mar 15; 123(Pt 6):861-70.
    View in: PubMed
  39. Nair RR, Emmons MF, Cress AE, Argilagos RF, Lam K, Kerr WT, Wang HG, Dalton WS, Hazlehurst LA. HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells. Mol Cancer Ther. 2009 Aug; 8(8):2441-51.
    View in: PubMed
  40. Wei J, Kitada S, Rega MF, Emdadi A, Yuan H, Cellitti J, Stebbins JL, Zhai D, Sun J, Yang L, Dahl R, Zhang Z, Wu B, Wang S, Reed TA, Wang HG, Lawrence N, Sebti S, Reed JC, Pellecchia M. Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2009 Apr; 8(4):904-13.
    View in: PubMed
  41. Takahashi Y, Meyerkord CL, Wang HG. Bif-1/endophilin B1: a candidate for crescent driving force in autophagy. Cell Death Differ. 2009 Jul; 16(7):947-55.
    View in: PubMed
  42. Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem. 2009 Apr 24; 284(17):11171-83.
    View in: PubMed
  43. Etxebarria A, Terrones O, Yamaguchi H, Landajuela A, Landeta O, Antonsson B, Wang HG, Basañez G. Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large scale membrane morphological rearrangements. J Biol Chem. 2009 Feb 13; 284(7):4200-12.
    View in: PubMed
  44. Coppola D, Khalil F, Eschrich SA, Boulware D, Yeatman T, Wang HG. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer. 2008 Nov 15; 113(10):2665-70.
    View in: PubMed
  45. Hu X, Sun J, Wang HG, Manetsch R. Bcl-XL-templated assembly of its own protein-protein interaction modulator from fragments decorated with thio acids and sulfonyl azides. J Am Chem Soc. 2008 Oct 22; 130(42):13820-1.
    View in: PubMed
  46. Meyerkord CL, Takahashi Y, Araya R, Takada N, Weiss RS, Wang HG. Loss of Hus1 sensitizes cells to etoposide-induced apoptosis by regulating BH3-only proteins. Oncogene. 2008 Dec 11; 27(58):7248-59.
    View in: PubMed
  47. Coppola D, Oliveri C, Sayegh Z, Boulware D, Takahashi Y, Pow-Sang J, Djeu JY, Wang HG. Bax-interacting factor-1 expression in prostate cancer. Clin Genitourin Cancer. 2008 Sep; 6(2):117-21.
    View in: PubMed
  48. Li CG, Gruidl M, Eschrich S, McCarthy S, Wang HG, Alexandrow MG, Yeatman TJ. Insig2 is associated with colon tumorigenesis and inhibits Bax-mediated apoptosis. Int J Cancer. 2008 Jul 15; 123(2):273-82.
    View in: PubMed
  49. Yamaguchi H, Woods NT, Dorsey JF, Takahashi Y, Gjertsen NR, Yeatman T, Wu J, Wang HG. SRC directly phosphorylates Bif-1 and prevents its interaction with Bax and the initiation of anoikis. J Biol Chem. 2008 Jul 4; 283(27):19112-8.
    View in: PubMed
  50. Oliveira V, Romanow WJ, Geisen C, Otterness DM, Mercurio F, Wang HG, Dalton WS, Abraham RT. A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis. J Biol Chem. 2008 May 9; 283(19):13174-84.
    View in: PubMed
  51. Sun A, Tang J, Hong Y, Song J, Terranova PF, Thrasher JB, Svojanovsky S, Wang HG, Li B. Androgen receptor-dependent regulation of Bcl-xL expression: Implication in prostate cancer progression. Prostate. 2008 Mar 1; 68(4):453-61.
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  52. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, Baba M, Baehrecke EH, Bahr BA, Ballabio A, Bamber BA, Bassham DC, Bergamini E, Bi X, Biard-Piechaczyk M, Blum JS, Bredesen DE, Brodsky JL, Brumell JH, Brunk UT, Bursch W, Camougrand N, Cebollero E, Cecconi F, Chen Y, Chin LS, Choi A, Chu CT, Chung J, Clarke PG, Clark RS, Clarke SG, Clavé C, Cleveland JL, Codogno P, Colombo MI, Coto-Montes A, Cregg JM, Cuervo AM, Debnath J, Demarchi F, Dennis PB, Dennis PA, Deretic V, Devenish RJ, Di Sano F, Dice JF, Difiglia M, Dinesh-Kumar S, Distelhorst CW, Djavaheri-Mergny M, Dorsey FC, Dröge W, Dron M, Dunn WA, Duszenko M, Eissa NT, Elazar Z, Esclatine A, Eskelinen EL, Fésüs L, Finley KD, Fuentes JM, Fueyo J, Fujisaki K, Galliot B, Gao FB, Gewirtz DA, Gibson SB, Gohla A, Goldberg AL, Gonzalez R, González-Estévez C, Gorski S, Gottlieb RA, Häussinger D, He YW, Heidenreich K, Hill JA, Høyer-Hansen M, Hu X, Huang WP, Iwasaki A, Jäättelä M, Jackson WT, Jiang X, Jin S, Johansen T, Jung JU, Kadowaki M, Kang C, Kelekar A, Kessel DH, Kiel JA, Kim HP, Kimchi A, Kinsella TJ, Kiselyov K, Kitamoto K, Knecht E, Komatsu M, Kominami E, Kondo S, Kovács AL, Kroemer G, Kuan CY, Kumar R, Kundu M, Landry J, Laporte M, Le W, Lei HY, Lenardo MJ, Levine B, Lieberman A, Lim KL, Lin FC, Liou W, Liu LF, Lopez-Berestein G, López-Otín C, Lu B, Macleod KF, Malorni W, Martinet W, Matsuoka K, Mautner J, Meijer AJ, Meléndez A, Michels P, Miotto G, Mistiaen WP, Mizushima N, Mograbi B, Monastyrska I, Moore MN, Moreira PI, Moriyasu Y, Motyl T, Münz C, Murphy LO, Naqvi NI, Neufeld TP, Nishino I, Nixon RA, Noda T, Nürnberg B, Ogawa M, Oleinick NL, Olsen LJ, Ozpolat B, Paglin S, Palmer GE, Papassideri I, Parkes M, Perlmutter DH, Perry G, Piacentini M, Pinkas-Kramarski R, Prescott M, Proikas-Cezanne T, Raben N, Rami A, Reggiori F, Rohrer B, Rubinsztein DC, Ryan KM, Sadoshima J, Sakagami H, Sakai Y, Sandri M, Sasakawa C, Sass M, Schneider C, Seglen PO, Seleverstov O, Settleman J, Shacka JJ, Shapiro IM, Sibirny A, Silva-Zacarin EC, Simon HU, Simone C, Simonsen A, Smith MA, Spanel-Borowski K, Srinivas V, Steeves M, Stenmark H, Stromhaug PE, Subauste CS, Sugimoto S, Sulzer D, Suzuki T, Swanson MS, Tabas I, Takeshita F, Talbot NJ, Tallóczy Z, Tanaka K, Tanaka K, Tanida I, Taylor GS, Taylor JP, Terman A, Tettamanti G, Thompson CB, Thumm M, Tolkovsky AM, Tooze SA, Truant R, Tumanovska LV, Uchiyama Y, Ueno T, Uzcátegui NL, van der Klei I, Vaquero EC, Vellai T, Vogel MW, Wang HG, Webster P, Wiley JW, Xi Z, Xiao G, Yahalom J, Yang JM, Yap G, Yin XM, Yoshimori T, Yu L, Yue Z, Yuzaki M, Zabirnyk O, Zheng X, Zhu X, Deter RL. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008 Feb; 4(2):151-75.
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  53. Woods NT, Yamaguchi H, Lee FY, Bhalla KN, Wang HG. Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res. 2007 Nov 15; 67(22):10744-52.
    View in: PubMed
  54. Takahashi Y, Meyerkord CL, Wang HG. BARgaining membranes for autophagosome formation: Regulation of autophagy and tumorigenesis by Bif-1/Endophilin B1. Autophagy. 2008 Jan; 4(1):121-4.
    View in: PubMed
  55. Vicente-Suarez I, Takahashi Y, Cheng F, Horna P, Wang HW, Wang HG, Sotomayor EM. Identification of a novel negative role of flagellin in regulating IL-10 production. Eur J Immunol. 2007 Nov; 37(11):3164-75.
    View in: PubMed
  56. Ren Y, Chen Z, Chen L, Woods NT, Reuther GW, Cheng JQ, Wang HG, Wu J. Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XL. J Biol Chem. 2007 Dec 14; 282(50):36463-73.
    View in: PubMed
  57. Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, Liang C, Jung JU, Cheng JQ, Mulé JJ, Pledger WJ, Wang HG. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007 Oct; 9(10):1142-51.
    View in: PubMed
  58. Azumi K, Sabau SV, Fujie M, Usami T, Koyanagi R, Kawashima T, Fujiwara S, Ogasawara M, Satake M, Nonaka M, Wang HG, Satou Y, Satoh N. Gene expression profile during the life cycle of the urochordate Ciona intestinalis. Dev Biol. 2007 Aug 15; 308(2):572-82.
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  59. Yamaguchi H, Wang HG. Tissue transglutaminase serves as an inhibitor of apoptosis by cross-linking caspase 3 in thapsigargin-treated cells. Mol Cell Biol. 2006 Jan; 26(2):569-79.
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  60. Takada N, Yamaguchi H, Shida K, Terajima D, Satou Y, Kasuya A, Satoh N, Satake M, Wang HG. The cell death machinery controlled by Bax and Bcl-XL is evolutionarily conserved in Ciona intestinalis. Apoptosis. 2005 Dec; 10(6):1211-20.
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  61. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ, Wang HG. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 2005 Nov; 25(21):9369-82.
    View in: PubMed
  62. Bali P, Pranpat M, Swaby R, Fiskus W, Yamaguchi H, Balasis M, Rocha K, Wang HG, Richon V, Bhalla K. Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2. Clin Cancer Res. 2005 Sep 1; 11(17):6382-9.
    View in: PubMed
  63. Zhang X, Li P, Bao J, Nicosia SV, Wang H, Enkemann SA, Bai W. Suppression of death receptor-mediated apoptosis by 1,25-dihydroxyvitamin D3 revealed by microarray analysis. J Biol Chem. 2005 Oct 21; 280(42):35458-68.
    View in: PubMed
  64. Yin H, Lee GI, Sedey KA, Kutzki O, Park HS, Orner BP, Ernst JT, Wang HG, Sebti SM, Hamilton AD. Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL. J Am Chem Soc. 2005 Jul 27; 127(29):10191-6.
    View in: PubMed
  65. Zheng Y, Yamaguchi H, Tian C, Lee MW, Tang H, Wang HG, Chen Q. Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene. 2005 May 5; 24(20):3339-47.
    View in: PubMed
  66. Yin H, Lee GI, Sedey KA, Rodriguez JM, Wang HG, Sebti SM, Hamilton AD. Terephthalamide derivatives as mimetics of helical peptides: disruption of the Bcl-x(L)/Bak interaction. J Am Chem Soc. 2005 Apr 20; 127(15):5463-8.
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  67. Araya R, Hirai I, Meyerkord CL, Wang HG. Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway. FEBS Lett. 2005 Jan 3; 579(1):157-61.
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  68. Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004 Oct 29; 279(44):45495-502.
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  69. Yamaguchi H, Chen J, Bhalla K, Wang HG. Regulation of Bax activation and apoptotic response to microtubule-damaging agents by p53 transcription-dependent and -independent pathways. J Biol Chem. 2004 Sep 17; 279(38):39431-7.
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  70. Hirai I, Sasaki T, Wang HG. Human hRad1 but not hRad9 protects hHus1 from ubiquitin-proteasomal degradation. Oncogene. 2004 Jul 1; 23(30):5124-30.
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  71. Terrones O, Antonsson B, Yamaguchi H, Wang HG, Liu J, Lee RM, Herrmann A, Basañez G. Lipidic pore formation by the concerted action of proapoptotic BAX and tBID. J Biol Chem. 2004 Jul 16; 279(29):30081-91.
    View in: PubMed
  72. Dan HC, Sun M, Kaneko S, Feldman RI, Nicosia SV, Wang HG, Tsang BK, Cheng JQ. Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem. 2004 Feb 13; 279(7):5405-12.
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  73. Terajima D, Yamada S, Uchino R, Ikawa S, Ikeda M, Shida K, Arai Y, Wang HG, Satoh N, Satake M. Identification and sequence of seventy-nine new transcripts expressed in hemocytes of Ciona intestinalis, three of which may be involved in characteristic cell-cell communication. DNA Res. 2003 Oct 31; 10(5):203-12.
    View in: PubMed
  74. Fuino L, Bali P, Wittmann S, Donapaty S, Guo F, Yamaguchi H, Wang HG, Atadja P, Bhalla K. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther. 2003 Oct; 2(10):971-84.
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  75. Lee MW, Hirai I, Wang HG. Caspase-3-mediated cleavage of Rad9 during apoptosis. Oncogene. 2003 Sep 25; 22(41):6340-6.
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  76. Chen T, Yang I, Irby R, Shain KH, Wang HG, Quackenbush J, Coppola D, Cheng JQ, Yeatman TJ. Regulation of caspase expression and apoptosis by adenomatous polyposis coli. Cancer Res. 2003 Aug 1; 63(15):4368-74.
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  77. Terajima D, Shida K, Takada N, Kasuya A, Rokhsar D, Satoh N, Satake M, Wang HG. Identification of candidate genes encoding the core components of the cell death machinery in the Ciona intestinalis genome. Cell Death Differ. 2003 Jun; 10(6):749-53.
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  78. Griffin D, Wittmann S, Guo F, Nimmanapalli R, Bali P, Wang HG, Bhalla K. Molecular determinants of epothilone B derivative (BMS 247550) and Apo-2L/TRAIL-induced apoptosis of human ovarian cancer cells. Gynecol Oncol. 2003 Apr; 89(1):37-47.
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  79. Yamaguchi H, Bhalla K, Wang HG. Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Cancer Res. 2003 Apr 1; 63(7):1483-9.
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  80. Yoshida K, Wang HG, Miki Y, Kufe D. Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. EMBO J. 2003 Mar 17; 22(6):1431-41.
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  81. Nimmanapalli R, O'Bryan E, Kuhn D, Yamaguchi H, Wang HG, Bhalla KN. Regulation of 17-AAG-induced apoptosis: role of Bcl-2, Bcl-XL, and Bax downstream of 17-AAG-mediated down-regulation of Akt, Raf-1, and Src kinases. Blood. 2003 Jul 1; 102(1):269-75.
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  82. Wittmann S, Bali P, Donapaty S, Nimmanapalli R, Guo F, Yamaguchi H, Huang M, Jove R, Wang HG, Bhalla K. Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis. Cancer Res. 2003 Jan 1; 63(1):93-9.
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  83. Dehal P, Satou Y, Campbell RK, Chapman J, Degnan B, De Tomaso A, Davidson B, Di Gregorio A, Gelpke M, Goodstein DM, Harafuji N, Hastings KE, Ho I, Hotta K, Huang W, Kawashima T, Lemaire P, Martinez D, Meinertzhagen IA, Necula S, Nonaka M, Putnam N, Rash S, Saiga H, Satake M, Terry A, Yamada L, Wang HG, Awazu S, Azumi K, Boore J, Branno M, Chin-Bow S, DeSantis R, Doyle S, Francino P, Keys DN, Haga S, Hayashi H, Hino K, Imai KS, Inaba K, Kano S, Kobayashi K, Kobayashi M, Lee BI, Makabe KW, Manohar C, Matassi G, Medina M, Mochizuki Y, Mount S, Morishita T, Miura S, Nakayama A, Nishizaka S, Nomoto H, Ohta F, Oishi K, Rigoutsos I, Sano M, Sasaki A, Sasakura Y, Shoguchi E, Shin-i T, Spagnuolo A, Stainier D, Suzuki MM, Tassy O, Takatori N, Tokuoka M, Yagi K, Yoshizaki F, Wada S, Zhang C, Hyatt PD, Larimer F, Detter C, Doggett N, Glavina T, Hawkins T, Richardson P, Lucas S, Kohara Y, Levine M, Satoh N, Rokhsar DS. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science. 2002 Dec 13; 298(5601):2157-67.
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  84. Yamaguchi H, Wang HG. Bcl-XL protects BimEL-induced Bax conformational change and cytochrome C release independent of interacting with Bax or BimEL. J Biol Chem. 2002 Nov 1; 277(44):41604-12.
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  85. Hirai I, Wang HG. A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex. J Biol Chem. 2002 Jul 12; 277(28):25722-7.
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  86. Yoshida K, Komatsu K, Wang HG, Kufe D. c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. Mol Cell Biol. 2002 May; 22(10):3292-300.
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  87. Guo F, Nimmanapalli R, Paranawithana S, Wittman S, Griffin D, Bali P, O'Bryan E, Fumero C, Wang HG, Bhalla K. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Blood. 2002 May 1; 99(9):3419-26.
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  88. Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang HG. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res. 2002 Jan 15; 62(2):466-71.
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  89. Cunnick JM, Meng S, Ren Y, Desponts C, Wang HG, Djeu JY, Wu J. Regulation of the mitogen-activated protein kinase signaling pathway by SHP2. J Biol Chem. 2002 Mar 15; 277(11):9498-504.
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  90. Yamaguchi H, Wang HG. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene. 2001 Nov 22; 20(53):7779-86.
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  91. Hirai I, Wang HG. Survival-factor-induced phosphorylation of Bad results in its dissociation from Bcl-x(L) but not Bcl-2. Biochem J. 2001 Oct 15; 359(Pt 2):345-52.
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  92. Cuddeback SM, Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S, Wang HG. Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J Biol Chem. 2001 Jun 8; 276(23):20559-65.
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  93. Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG. PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition. Oncogene. 2000 Nov 2; 19(46):5291-7.
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  94. Komatsu K, Hopkins KM, Lieberman HB, Wang H. Schizosaccharomyces pombe Rad9 contains a BH3-like region and interacts with the anti-apoptotic protein Bcl-2. FEBS Lett. 2000 Sep 15; 481(2):122-6.
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  95. Neshat MS, Raitano AB, Wang HG, Reed JC, Sawyers CL. The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and -independent pathways: roles for phosphatidylinositol 3-kinase and Raf. Mol Cell Biol. 2000 Feb; 20(4):1179-86.
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  96. Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG. Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nat Cell Biol. 2000 Jan; 2(1):1-6.
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  97. Schürmann A, Mooney AF, Sanders LC, Sells MA, Wang HG, Reed JC, Bokoch GM. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol. 2000 Jan; 20(2):453-61.
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  98. James HJ, Sharer LR, Zhang Q, Wang HG, Epstein LG, Reed JC, Gelbard HA. Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. Neuropathol Appl Neurobiol. 1999 Oct; 25(5):380-6.
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  99. Chen W, Wang HG, Srinivasula SM, Alnemri ES, Cooper NR. B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway. J Immunol. 1999 Sep 1; 163(5):2483-91.
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  100. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science. 1999 Apr 9; 284(5412):339-43.
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  101. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 1999 Jan 25; 144(2):281-92.
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  102. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang HG, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood. 1998 May 1; 91(9):3379-89.
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  103. Wang HG, Reed JC. Mechanisms of Bcl-2 protein function. Histol Histopathol. 1998 Apr; 13(2):521-30.
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  104. Kitada S, Krajewska M, Zhang X, Scudiero D, Zapata JM, Wang HG, Shabaik A, Tudor G, Krajewski S, Myers TG, Johnson GS, Sausville EA, Reed JC. Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines. Am J Pathol. 1998 Jan; 152(1):51-61.
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  105. Wang HG, Reed JC. Bc1-2, Raf-1 and mitochondrial regulation of apoptosis. Biofactors. 1998; 8(1-2):13-6.
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  106. Zapata JM, Krajewska M, Krajewski S, Huang RP, Takayama S, Wang HG, Adamson E, Reed JC. Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors. Breast Cancer Res Treat. 1998 Jan; 47(2):129-40.
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  107. Chhanabhai M, Krajewski S, Krajewska M, Wang HG, Reed JC, Gascoyne RD. Immunohistochemical analysis of interleukin-1beta-converting enzyme/Ced-3 family protease, CPP32/Yama/Caspase-3, in Hodgkin's disease. Blood. 1997 Sep 15; 90(6):2451-5.
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  108. Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, Fassy F, Reed JC, Kroemer G. The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. J Exp Med. 1997 Jul 7; 186(1):25-37.
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  109. Krajewski S, Gascoyne RD, Zapata JM, Krajewska M, Kitada S, Chhanabhai M, Horsman D, Berean K, Piro LD, Fugier-Vivier I, Liu YJ, Wang HG, Reed JC. Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood. 1997 May 15; 89(10):3817-25.
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  110. Keane RW, Srinivasan A, Foster LM, Testa MP, Ord T, Nonner D, Wang HG, Reed JC, Bredesen DE, Kayalar C. Activation of CPP32 during apoptosis of neurons and astrocytes. J Neurosci Res. 1997 Apr 15; 48(2):168-80.
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  111. Krajewska M, Wang HG, Krajewski S, Zapata JM, Shabaik A, Gascoyne R, Reed JC. Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer Res. 1997 Apr 15; 57(8):1605-13.
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  112. Perry DK, Smyth MJ, Wang HG, Reed JC, Duriez P, Poirier GG, Obeid LM, Hannun YA. Bcl-2 acts upstream of the PARP protease and prevents its activation. Cell Death Differ. 1997 Jan; 4(1):29-33.
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  113. Wang HG, Rapp UR, Reed JC. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell. 1996 Nov 15; 87(4):629-38.
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  114. Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A. 1996 Jul 9; 93(14):7063-8.
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  115. Zhang Z, Vuori K, Wang H, Reed JC, Ruoslahti E. Integrin activation by R-ras. Cell. 1996 Apr 5; 85(1):61-9.
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  116. Liu Y, Lee MO, Wang HG, Li Y, Hashimoto Y, Klaus M, Reed JC, Zhang X. Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol Cell Biol. 1996 Mar; 16(3):1138-49.
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  117. Lin EY, Orlofsky A, Wang HG, Reed JC, Prystowsky MB. A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood. 1996 Feb 1; 87(3):983-92.
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  118. Yagihashi S, Yamagishi S, Wada R, Sugimoto K, Baba M, Wong HG, Fujimoto J, Nishimura C, Kokai Y. Galactosemic neuropathy in transgenic mice for human aldose reductase. Diabetes. 1996 Jan; 45(1):56-9.
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  119. Reed JC, Miyashita T, Takayama S, Wang HG, Sato T, Krajewski S, Aimé-Sempé C, Bodrug S, Kitada S, Hanada M. BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem. 1996 Jan; 60(1):23-32.
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  120. Reed JC, Miyashita T, Krajewski S, Takayama S, Aime-Sempe C, Kitada S, Sato T, Wang HG, Harigai M, Hanada M, Krajewska M, Kochel K, Millan J, Kobayashi H. Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma. Cancer Treat Res. 1996; 84:31-72.
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  121. Reed JC, Zha H, Aime-Sempe C, Takayama S, Wang HG. Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death. Adv Exp Med Biol. 1996; 406:99-112.
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  122. Martin SJ, Newmeyer DD, Mathias S, Farschon DM, Wang HG, Reed JC, Kolesnick RN, Green DR. Cell-free reconstitution of Fas-, UV radiation- and ceramide-induced apoptosis. EMBO J. 1995 Nov 1; 14(21):5191-200.
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  123. Wang HG, Millan JA, Cox AD, Der CJ, Rapp UR, Beck T, Zha H, Reed JC. R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism. J Cell Biol. 1995 May; 129(4):1103-14.
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  124. Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol. 1994 Dec; 145(6):1323-36.
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  125. Krajewski S, Krajewska M, Shabaik A, Wang HG, Irie S, Fong L, Reed JC. Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res. 1994 Nov 1; 54(21):5501-7.
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  126. Sato T, Hanada M, Bodrug S, Irie S, Iwama N, Boise LH, Thompson CB, Golemis E, Fong L, Wang HG, et al. Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci U S A. 1994 Sep 27; 91(20):9238-42.
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  127. Wang HG, Miyashita T, Takayama S, Sato T, Torigoe T, Krajewski S, Tanaka S, Hovey L, Troppmair J, Rapp UR, et al. Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene. 1994 Sep; 9(9):2751-6.
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  128. Selvakumaran M, Lin HK, Miyashita T, Wang HG, Krajewski S, Reed JC, Hoffman B, Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 1994 Jun; 9(6):1791-8.
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  129. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994 Jun; 9(6):1799-805.
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