HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 36, 26562-26568, September 8, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/36/26562    most recent M605391200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okumura, K. Articles by Furnari, F. B. Search for Related Content PubMed PubMed Citation Articles by Okumura, K. Articles by Furnari, F. B. Related Collections Papers Of The Week Social Bookmarking                      What's this?

PCAF Modulates PTEN Activity^*

Koichi Okumura, Michelle Mendoza, Robert M. Bachoo^¶, Ronald A. DePinho^||**, Webster K. Cavenee, and Frank B. Furnari¹

From the Ludwig Institute for Cancer Research, San Diego Branch, Biomedical Sciences Graduate Program, Center for Molecular Genetics, Department of Medicine and Cancer Center, University of California at San Diego, La Jolla, California 92093-0660, the ^¶Departments of Neurology and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, and the ^||Department of Medical Oncology and ^**Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts 02115

The PTEN protein has a single catalytic domain possessing both lipid phosphoinositol and protein phosphatase activities. The lipid phosphoinositol phosphatase activity is essential for PTEN to block the cell cycle in the G₁ phase and thereby to suppress tumor formation and progression (Cantley, L. C., and Neel, B. G. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 4240-4245), although the mechanisms governing PTEN activity under normal and neoplastic growth conditions remain unclear. Here, we report that PTEN interacts physically and functionally with PCAF, a histone acetyltransferase that regulates gene transcription through interaction with p300/CBP and various sequencespecific transcription factors (Nakatani, Y. (2001) Genes Cells 6, 79-86). Expression of PCAF results in increased acetylation of lysine residues (Lys¹²⁵ and Lys¹²⁸) within the catalytic cleft of PTEN, a structure essential for phosphatidylinositol 3,4,5-trisphosphate specificity (Lee, J. O., Yang, H., Georgescu, M. M., Di Cristofano, A., Maehama, T., Shi, Y., Dixon, J. E., Pandolfi, P., and Pavletich, N. P. (1999) Cell 99, 323-334). The acetylation of PTEN caused by PCAF expression depends on the presence of growth factors. Reduction of endogenous PCAF activity using shRNA results in a loss of PTEN acetylation in response to growth factors and restores the ability of PTEN to down-regulate phosphatidylinositol 3-kinase signaling and to induce G₁ cell cycle arrest. The retention of phosphatidylinositol 3-kinase/AKT signaling and cell cycle regulatory activities of acetylationresistant PTEN K125R and K128R mutants in the presence of enforced PCAF expression suggest a causal relationship. Together, these findings indicate a mechanism of PTEN regulation that forges a link between distinct cancer-relevant pathways central to the control of growth factor signaling and gene expression.

Received for publication, June 5, 2006 , and in revised form, July 6, 2006.

^* This work was supported in part by Scholar Awards for cancer research from the Kimmel Foundation and the V Foundation (to F. B. F.), Grant CA95616 from the National Cancer Institute (to W. K. C., R. M. B., F. B. F., and R. A. D.), and by a Fellow Award from the National Foundation for Cancer Research (to W. K. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article was selected as a Paper of the Week.

¹ To whom correspondence should be addressed. Tel.: 858-534-7819; Fax: 858-534-7750; E-mail: ffurnari{at}ucsd.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Ikenoue, K. Inoki, B. Zhao, and K.-L. Guan PTEN Acetylation Modulates Its Interaction with PDZ Domain Cancer Res., September 1, 2008; 68(17): 6908 - 6912. [Abstract] [Full Text] [PDF]

				S. Roy, R. Jeffrey, and M. Tenniswood Array-based analysis of the effects of trichostatin A and CG-1521 on cell cycle and cell death in LNCaP prostate cancer cells Mol. Cancer Ther., July 1, 2008; 7(7): 1931 - 1939. [Abstract] [Full Text] [PDF]

				X.-H. Yao and B. L. G. Nyomba Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1797 - R1806. [Abstract] [Full Text] [PDF]

				N. Dey, H. E. Crosswell, P. De, R. Parsons, Q. Peng, J. D. Su, and D. L. Durden The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration Cancer Res., March 15, 2008; 68(6): 1862 - 1871. [Abstract] [Full Text] [PDF]

				T. Tamguney and D. Stokoe New insights into PTEN J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079. [Abstract] [Full Text] [PDF]

				E. D. Eliseeva, V. Valkov, M. Jung, and M. O. Jung Characterization of novel inhibitors of histone acetyltransferases Mol. Cancer Ther., September 1, 2007; 6(9): 2391 - 2398. [Abstract] [Full Text] [PDF]

				S. Roy and M. Tenniswood Site-specific Acetylation of p53 Directs Selective Transcription Complex Assembly J. Biol. Chem., February 16, 2007; 282(7): 4765 - 4771. [Abstract] [Full Text] [PDF]

				D. F. Barber, M. Alvarado-Kristensson, A. Gonzalez-Garcia, R. Pulido, and A. C. Carrera PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase Sci. Signal., November 21, 2006; 2006(362): pe49 - pe49. [Abstract] [Full Text] [PDF]