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NMR Structure of CBP Bromodomain in complex with p53 peptide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Blue-cone monochromacy OMIM:[303900], Breast cancer OMIM:[191170], Colorblindness, protan OMIM:[303900], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Rubenstein-Taybi syndrome OMIM:[600140], Thyroid carcinoma OMIM:[191170]

About this Structure

1JSP is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation., Mujtaba S, He Y, Zeng L, Yan S, Plotnikova O, Sachchidanand, Sanchez R, Zeleznik-Le NJ, Ronai Z, Zhou MM, Mol Cell. 2004 Jan 30;13(2):251-63. PMID:14759370

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