Research article summary (published 30 Aug 2009):

KLF4 suppresses HDACi induced caspase activation and the SAPK pathway by targeting p57(Kip2).

Full Abstract

Kruppel-like factor 4 (KLF4) belongs to a family of evolutionarily conserved zinc finger-containing transcription factors. It has been shown to mediate self renewal and pluripotency, regulate adipogenesis and play a critical role in monocyte differentiation. KLF4 is also highly expressed in squamous cell carcinomas and in 70% of all primary human breast cancers, suggesting a putative role for KLF4 as being an oncogene and as an antiapoptotic factor. However, the mechanism of this regulation remains unclear. Here, we show that KLF4 is induced during histone deacetylase inhibitor treatment, and regulates the extrinsic apoptosis pathway by inhibiting caspase cleavage. In addition, KLF4 binds to the p57(Kip2) promoter and transcriptionally upregulates its expression, which in turn inhibits the stress activated protein kinase cascade and c-Jun phosphorylation. Our findings indicate that in cancer cells that express high levels of KLF4 may be refractory to HDACi treatment. Results of our study demonstrate an unexpected antiapoptotic function of KLF4, and suggest an important cell fate determinant following histone deacetylase inhibitor induced apoptosis.

Author information

Author/s: Ky, Nung (N); Lim, Chuan Bian (CB); Li, Jinming (J); Tam, James P (JP); Hamza, Mohamed Sabry (MS); Zhao, Yan (Y);

Affiliation: Nanyang Technological University, Singapore, Singapore.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Apoptosis : an international journal on programmed cell death (Apoptosis), published in United States. (Language: eng)

Reference: 2009-Sep; vol 14 (issue 9) : pp 1095-107

Dates: Created 2009/08/06; Completed 2009/10/21;

PMID: 19544095, status: MEDLINE (last retrieved date: 10/21/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Apoptosis - drug effects Caspases - metabolism Cyclin-Dependent Kinase Inhibitor p57 - genetics; metabolism Cytoprotection - drug effects Enzyme Activation - drug effects HCT116 Cells Histone Deacetylases - antagonists & inhibitors Humans

Hydroxamic Acids - pharmacology Kruppel-Like Transcription Factors - metabolism MAP Kinase Signaling System - drug effects Mitogen-Activated Protein Kinases - metabolism Oligopeptides - pharmacology Phosphorylation - drug effects Promoter Regions, Genetic - genetics Protein Binding - drug effects

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: CDKN1C protein, human (0) ; Cyclin-Dependent Kinase Inhibitor p57 (0) ; GKLF protein (0) ; Hydroxamic Acids (0) ; Kruppel-Like Transcription Factors (0) ; Oligopeptides (0) ; benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone (0) ; vorinostat (149647-78-9) ; Mitogen-Activated Protein Kinases (EC 2.7.1.37) ; Caspases (EC 3.4.22.-) ; Histone Deacetylases (EC 3.5.1.-)

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