The p53 C Terminus Controls Site-Specific DNA Binding and Promotes Structural Changes within the Central DNA Binding Domain

Oleg Laptenko, Idit Shiff, Will Freed-Pastor, Andrew Zupnick, Melissa Mattia, Ella Freulich, Inbal Shamir, Noam Kadouri, Tamar Kahan, James Manfredi, Itamar Simon, Carol Prives

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

DNA binding by numerous transcription factors including the p53 tumor suppressor protein constitutes a vital early step in transcriptional activation. While the role of the central core DNA binding domain (DBD) of p53 in site-specific DNA binding has been established, the contribution of the sequence-independent C-terminal domain (CTD) is still not well understood. We investigated the DNA-binding properties of a series of p53 CTD variants using a combination of invitro biochemical analyses and invivo binding experiments. Our results provide several unanticipated and interconnected findings. First, the CTD enables DNA binding in a sequence-dependent manner that is drastically altered by either its modification or deletion. Second, dependence on the CTD correlates with the extent to which the p53 binding site deviates from the canonical consensus sequence. Third, the CTD enables stable formation of p53-DNA complexes to divergent binding sites via DNA-induced conformational changes within the DBD itself.

Original languageEnglish
Pages (from-to)1034-1046
Number of pages13
JournalMolecular Cell
Volume57
Issue number6
DOIs
StatePublished - 19 Mar 2015

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