title: Chromatin remodelling protein SMAR1 inhibits p53 dependent transactivation by regulating acetyl transferase p300.
abstract: Acetylation of p53 is indispensable for its transcriptional activities and induction of apoptosis upon DNA damage. Here, we show that chromatin remodelling protein SMAR1 inhibits p53 acetylation and p53 dependent apoptosis by repressing p300 expression in response to DNA damage. The repression of p300 expression by SMAR1 is relieved upon treatment with proteosomal inhibitors MG132 and Lactacystin. We demonstrate that SMAR1 interacts with p53-p300 transcriptional complex and SMAR1 overexpression antagonizes p300 interaction with p53 and suppresses activation of p53 apoptotic targets and p53 regulated miRNA miR-34a. Conversely, knockdown of SMAR1 promotes p300 accumulation and p53 acetylation while ectopic expression of p300 rescues SMAR1 inhibition on p53. Collectively, these results indicate that SMAR1 is an important player in p300-p53 regulated DNA damage signalling pathway and can exert its effect on apoptosis in a transcription independent manner.
authors.affiliation: National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Sinha
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Malonia
authors.forename: Smriti P K
authors.initials: SP
authors.lastname: Mittal
authors.forename: Jinumary
authors.initials: J
authors.lastname: Mathai
authors.forename: Jayanta K
authors.initials: JK
authors.lastname: Pal
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C417914:BANP protein, human; C495901:TP53 protein, human