Deacetylation of p53 modulates its effect on cell growth and apoptosis

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The p53 tumour suppressor is a transcriptional factor whose activity is modulated by protein stability and post-translational modifications including acetylation1,2,3,4. The mechanism by which acetylated p53 is maintained in vivo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purified a p53 target protein in the deacetylase complexes (designated PID; but identical to metastasis-associated protein 2 (MTA2)), which has been identified as a component of the NuRD complex5,6,7. PID specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. These results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.

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Figure 1: Indirect interactions between p53 and HDAC1, and purification of PID.
Figure 2: PID interacts with p53 both in vitro and in vivo.
Figure 3: PID is involved in p53 deacetylation.
Figure 4: PID repression of transcription activation mediated by wild-type p53, Gal–VP16, or p53(K–R) mutant in cells.
Figure 5: The effects of PID on p53-mediated cell growth arrest, endogenous p21 activation and apopotosis.


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We thank R. Dalla-Favera, R. Baer and B. Tycko for critical discussions, and use of laboratory space and reagents; K. Vousden, B. Vogelstein, A. Levine, M. Oren, Y. Xiong, C. Hassig, S. L. Schreiber, S. Chellappan, G. Lozano and P. P. Pandolfi for antibodies, cell lines and plasmids; J. Qin, W. Wang and Y. Zhang for help; G. Cattoretti and H. Niu for suggestions in apoptosis assays; the sequencing facility of Columbia University Cancer Center for sequencing; F. Huang, M. Li, A. Nikolaev and N. A. Papanikolaou for sharing unpublished data and critical comment; and R.G. Roeder for continuous support and encouragement. This work was supported in part by grants from the NIH/NCI, the American Cancer Society and the Herbert Irving Comprehensive Cancer Center to W.G.

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  1. Correspondence and requests for material should be addressed to W.G. (e-mail: The GenBank accession number for the PID sequence is AF295807.

    • Wei Gu

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