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Molecular and Cellular Biology, January 2008, p. 448-456, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.00983-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Serine 15 Phosphorylation of p53 Directs Its Interaction with B56{gamma} and the Tumor Suppressor Activity of B56{gamma}-Specific Protein Phosphatase 2A{triangledown} ,{dagger}

Geoffrey P. Shouse, Xin Cai, and Xuan Liu*

Department of Biochemistry, University of California, Riverside, California 92521

Received 4 June 2007/ Returned for modification 20 July 2007/ Accepted 19 October 2007

Earlier studies have demonstrated a functional link between B56{gamma}-specific protein phosphatase 2A (B56{gamma}-PP2A) and p53 tumor suppressor activity. Upon DNA damage, a complex including B56{gamma}-PP2A and p53 is formed which leads to Thr55 dephosphorylation of p53, induction of the p53 transcriptional target p21, and the inhibition of cell proliferation. Although an enhanced interaction between p53 and B56{gamma} is observed after DNA damage, the underlying mechanism and its significance in PP2A tumor-suppressive function remain unclear. In this study, we show that the increased interaction between B56{gamma} and p53 after DNA damage requires ATM-dependent phosphorylation of p53 at Ser15. In addition, we demonstrate that the B56{gamma}3-induced inhibition of cell proliferation, induction of cell cycle arrest in G1, and blockage of anchorage-independent growth are also dependent on Ser15 phosphorylation of p53 and p53-B56{gamma} interaction. Taken together, our results provide a mechanistic link between Ser15 phosphorylation-mediated p53-B56{gamma} interaction and the modulation of p53 tumor suppressor activity by PP2A. We also show an important link between ATM activity and the tumor-suppressive function of B56{gamma}-PP2A.

* Corresponding author. Mailing address: Department of Biochemistry, University of California, Riverside, CA 92521. Phone: (951) 827-4350. Fax: (951) 827-4434. E-mail: xuan.liu{at}ucr.edu

{triangledown} Published ahead of print on 29 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2008, p. 448-456, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.00983-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kim, T.-S., Kim, H. D., Shin, H.-S., Kim, J. (2009). Phosphorylation Status of Nuclear Ribosomal Protein S3 Is Reciprocally Regulated by Protein Kinase C{delta} and Protein Phosphatase 2A. J. Biol. Chem. 284: 21201-21208 [Abstract] [Full Text]  
  • Mi, J., Bolesta, E., Brautigan, D. L., Larner, J. M. (2009). PP2A regulates ionizing radiation-induced apoptosis through Ser46 phosphorylation of p53. Molecular Cancer Therapeutics 8: 135-140 [Abstract] [Full Text]  
  • Cai, X., Liu, X. (2008). Inhibition of Thr-55 phosphorylation restores p53 nuclear localization and sensitizes cancer cells to DNA damage. Proc. Natl. Acad. Sci. USA 105: 16958-16963 [Abstract] [Full Text]  


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