title: c-MYC suppresses BIN1 to release poly(ADP-ribose) polymerase 1: a mechanism by which cancer cells acquire cisplatin resistance.
abstract: Cancer cells acquire resistance to DNA-damaging therapeutic agents, such as cisplatin, but the genetic mechanisms through which this occurs remain unclear. We show that the c-MYC oncoprotein increases cisplatin resistance by decreasing production of the c-MYC inhibitor BIN1 (bridging integrator 1). The sensitivity of cancer cells to cisplatin depended on BIN1 abundance, regardless of the p53 gene status. BIN1 bound to the automodification domain of and suppressed the catalytic activity of poly(ADP-ribose) polymerase 1 (PARP1, EC 2.4.2.30), an enzyme essential for DNA repair, thereby reducing the stability of the genome. The inhibition of PARP1 activity was sufficient for BIN1 to suppress c-MYC-mediated transactivation, the G(2)-M transition, and cisplatin resistance. Conversely, overexpressed c-MYC repressed BIN1 expression by blocking its activation by the MYC-interacting zinc finger transcription factor 1 (MIZ1) and thereby released PARP1 activity. Thus, a c-MYC-mediated positive feedback loop may contribute to cancer cell resistance to cisplatin.
authors: Molecular Signaling Program, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors: Slovénie
authors: S
authors: Pyndiah
authors: Satoshi
authors: S
authors: Tanida
authors: Kazi M
authors: KM
authors: Ahmed
authors: Erica K
authors: EK
authors: Cassimere
authors: Chungyoul
authors: C
authors: Choe
authors: Daitoku
authors: D
authors: Sakamuro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C101410:BIN1 protein, human; C109221:Bin1 protein, mouse; C489427:MYC protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; C485521:Miz1 protein, mouse; D044767:Ubiquitin-Protein Ligases; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin