Molecular Biology

Remodeling p53

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Science  17 Aug 2001:
Vol. 293, Issue 5533, pp. 1223
DOI: 10.1126/science.293.5533.1223b

About half of all human cancers contain mutations in the p53 tumor suppressor gene. In response to certain forms of cellular stress, the p53 protein induces cell cycle arrest by sequence-specific DNA binding and transcriptional activation of key target genes. Previous studies used purified DNA consensus sequences to produce a model in which p53 acquires DNA binding activity only after its carboxyl-terminal region is modified.

Using a chromatin-based assay that may better mimic the substrates p53 encounters in the cell nucleus, Espinosa and Emerson arrive at a very different model of how p53 regulates transcription. Studying the chromatin-assembled p21/WAF1 promoter, they find that unmodified p53 does bind DNA/chromatin and requires the same carboxyl-terminal region that was previously thought to repress DNA binding. The chromatin-bound p53 recruits a histone acetyltransferase (p300) to the promoter, which then acetylates the p53-bound nucleosomes, perhaps facilitating interaction with other components of the transcriptional machinery. Whether p53 uses the same or different mechanisms to regulate expression of its many other target genes is an important question that remains to be investigated. — PAK

Mol. Cell8, 57 (2001).

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