Reciprocal Interference Between the Sequence-specific Core and Nonspecific C-terminal DNA Binding Domains of P53: Implications for Regulation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1997 Oct 29

PMID 9343386

Citations 39

Authors

M E Anderson

B Woelker

M Reed

P Wang

P Tegtmeyer

Affiliations

Soon will be listed here.

Abstract

The tumor suppressor p53 has two DNA binding domains: a central sequence-specific domain and a C-terminal sequence-independent domain. Here, we show that binding of large but not small DNAs by the C terminus of p53 negatively regulates sequence-specific DNA binding by the central domain. Four previously described mechanisms for activation of specific DNA binding operate by blocking negative regulation. Deletion of the C terminus of p53 activates specific DNA binding only in the presence of large DNA. Three activator molecules (a small nucleic acid, a monoclonal antibody against the p53 C terminus, and a C-terminal peptide of p53) stimulate sequence-specific DNA binding only in the presence of both large DNA and p53 with an intact C terminus. Our findings argue that interactions of the C terminus of p53 with genomic DNA in vivo would prevent p53 binding to specific promoters and that cellular mechanisms to block C-terminal DNA binding would be required.

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