title: JunD-mediated repression of GADD45α and γ regulates escape from cell death in prostate cancer.
abstract: The AP-1 transcription factor complex has been implicated in a variety of biological processes including cell differentiation, proliferation, apoptosis and oncogenic transformation. We previously established that activation of the AP-1 family member JunD contributes to deregulated expression of the anti-apoptotic IL-6 gene in prostate cancer cells. We now show that inhibition of JunD in prostate cancer cells results in GADD45α- and γ-dependent induction of cell death and inhibition of tumor growth that is mediated at least partially via c-Jun N-terminal kinase (JNK) and p38 kinase activation. Apoptosis induction by dominant negative JunD and JNK and p38 kinase activation are impeded upon knock down of GADD45α and γ expression by small interfering RNA, most vividly demonstrating the central role of GADD45α and γ in JunD-mediated escape of prostate cancer cells from programmed cell death.
authors: International Center for Genetic Engineering and Biotechnology (ICGEB), Cancer Genomics Group, Cape Town, South Africa. luiz.zerbini@uct.ac.za
authors: Luiz Fernando
authors: LF
authors: Zerbini
authors: Jaíra Ferreira
authors: JF
authors: de Vasconcellos
authors: Akos
authors: A
authors: Czibere
authors: Yihong
authors: Y
authors: Wang
authors: Juliano D
authors: JD
authors: Paccez
authors: Xuesong
authors: X
authors: Gu
authors: Jin-Rong
authors: JR
authors: Zhou
authors: Towia A
authors: TA
authors: Libermann
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D048055:Mitogen-Activated Protein Kinase 8; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C485654:GADD45G protein, human; C559371:JunD protein, human