| First Author | Mujtaba S | Year | 2004 |
| Journal | Mol Cell | Volume | 13 |
| Issue | 2 | Pages | 251-63 |
| PubMed ID | 14759370 | Mgi Jnum | J:306714 |
| Mgi Id | MGI:6718243 | Doi | 10.1016/s1097-2765(03)00528-8 |
| Citation | Mujtaba S, et al. (2004) Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 13(2):251-63 |
| abstractText | Lysine acetylation of the tumor suppressor protein p53 in response to a wide variety of cellular stress signals is required for its activation as a transcription factor that regulates cell cycle arrest, senescence, or apoptosis. Here, we report that the conserved bromo-domain of the transcriptional coactivator CBP (CREB binding protein) binds specifically to p53 at the C-terminal acetylated lysine 382. This bromodomain/acetyl-lysine binding is responsible for p53 acetylation-dependent coactivator recruitment after DNA damage, a step essential for p53-induced transcriptional activation of the cyclin-dependent kinase inhibitor p21 in G1 cell cycle arrest. We further present the three-dimensional nuclear magnetic resonance structure of the CBP bromodomain in complex with a lysine 382-acetylated p53 peptide. Using structural and biochemical analyses, we define the molecular determinants for the specificity of this molecular recognition. |
