Cabin1 restrains p53 activity on chromatin.
The tumor suppressor p53 has been proposed to bind target promoters upon genotoxic stress. However, recent evidence shows that p53 occupies some target promoters without such stress, suggesting that a negative regulator might render p53 transcriptionally inactive on these promoters. Here we show that calcineurin binding protein 1 (Cabin1) is a negative regulator of p53. Downregulation of Cabin1 induces activation of a subset of p53 target genes. Cabin1 physically interacts with p53 on these target promoters and represses p53 transcriptional activity in the absence of genotoxic stress, by regulating histone modification and p53 acetylation marks. Knockdown of Cabin1 retards cell growth and promotes cell death after DNA damage in a p53-dependent manner. Thus, Cabin1 inhibits p53 function on chromatin in the quiescent state; the presence of inactive p53 on some promoters might allow a prompt response upon DNA damage.
Jang
Hyonchol
H
National Research Laboratory for Metabolic Checkpoint, Department of Biomedical Sciences & Biochemistry, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Choi
Soo-Youn
SY
Cho
Eun-Jung
EJ
Youn
Hong-Duk
HD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D004249:DNA Damage; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; C113151:Cabin1 protein, mouse; D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D019703:Calcineurin