This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Li, D. Articles by Friedman, S. L. Search for Related Content PubMed PubMed Citation Articles by Li, D. Articles by Friedman, S. L.

Regulation of Krüppel-like Factor 6 Tumor Suppressor Activity by Acetylation

¹ Division of Liver Diseases, Department of Medicine; and Departments of ² Human Genetics and ³ Pediatrics, Mount Sinai School of Medicine, New York, New York

Requests for reprints: Scott L. Friedman, Mount Sinai School of Medicine, Box 1123, 1425 Madison Avenue, Room 11-70C, New York, NY 10029-6574. Phone: 212-659-9501; Fax: 212-849-2574; E-mail: Scott.Friedman{at}mssm.edu.

Krüppel-like factor 6 (KLF6) is a zinc finger transcription factor and tumor suppressor that is inactivated in a number of human cancers by mutation, allelic loss, and/or promoter methylation. A key mechanism of growth inhibition by wild-type KLF6 is through p53-independent up-regulation of p21^WAF1/cip1 (CDKN1A), which is abrogated in several tumor-derived mutants. Here we show by chromatin immunoprecipitation that transactivation of p21^WAF1/cip1 by KLF6 occurs through its direct recruitment to the p21^WAF1/cip1 promoter and requires acetylation by histone acetyltransferase activity of either cyclic AMP–responsive element binding protein–binding protein or p300/CBP-associated factor. Direct lysine acetylation of KLF6 peptides can be shown by mass spectrometry. A single lysine-to-arginine point mutation (K209R) derived from prostate cancer reduces acetylation of KLF6 and abrogates its capacity to up-regulate endogenous p21^WAF1/cip1 and reduce cell proliferation. These data indicate that acetylation may regulate KLF6 function, and its loss in some tumor-derived mutants could contribute to its failure to suppress growth in prostate cancer.

This article has been cited by other articles:

				X. Huang, X. Li, and B. Guo KLF6 Induces Apoptosis in Prostate Cancer Cells through Up-regulation of ATF3 J. Biol. Chem., October 31, 2008; 283(44): 29795 - 29801. [Abstract] [Full Text] [PDF]

				P. M. Evans, W. Zhang, X. Chen, J. Yang, K. K. Bhakat, and C. Liu Kruppel-like Factor 4 Is Acetylated by p300 and Regulates Gene Transcription via Modulation of Histone Acetylation J. Biol. Chem., November 23, 2007; 282(47): 33994 - 34002. [Abstract] [Full Text] [PDF]