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 language | American English |
|---|---|
| Pages (from-to) | 1034-1046 |
| Number of pages | 13 |
| Journal | Molecular Cell |
| Volume | 57 |
| Issue number | 6 |
| DOIs | |
| State | Published - 19 Mar 2015 |
Bibliographical note
Funding Information:We thank members of the C.P. laboratory for valuable comments and suggestions. We are particularly grateful to Dr. S. Borukhov (Rowan University, NJ) for valuable advice and stimulating discussions. This work was supported by National Cancer Institute (NCI) grant CA77742. The work in the laboratory of I.S. was supported by the German-Israeli Foundation for Scientific Research and Development (grant 998/2008), the Israel Cancer Society, the Israel Cancer Research Foundation, and the Weinkselbaum Family Medical Research Fund.
Publisher Copyright:
© 2015 Elsevier Inc.