SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity.
The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, SIRT1 binds to p53 while repressing the expression of their target genes. Here, we report that SIRT1 also binds to p73 and suppresses p73-dependent transcriptional activity. SIRT1 in human cells reduces the transcriptional activity of p73, and partly inhibits apoptosis induced by p73. Furthermore, SIRT1 can deacetylate p73 protein acetylation both in vivo and in vitro. Collectively, these data suggest that SIRT1 can modulate p73 activity via deacetylation.
Dai
Jin Ming
JM
Beijing Institute of Radiation Medicine, Beijing, China.
Wang
Zhi Yan
ZY
Sun
Dao Chun
DC
Lin
Ru Xian
RX
Wang
Sheng Qi
SQ
D000107:Acetylation; D017209:Apoptosis / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005720:Gamma Rays; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases; D009536:Niacinamide / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D013267:Stilbenes; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D009536:Niacinamide; D008156:Luciferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol