An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation

Martin E Fernandez-Zapico, Ann Mladek, Volker Ellenrieder, Emma Folch-Puy, Laurence J Miller, Raul Urrutia

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

KLF11 is a biochemical paradigm for a subset of proteins that repress transcription via a Mad1-like mSin3A interacting domain (SID). The biological role of these proteins and the significance of their biochemical activity, however, remain to be established. We report that KLF11 is downregulated in human cancers, inhibits cell growth in vitro and in vivo, and suppresses neoplastic transformation. Transgenic mice for KLF11 display a downregulation of genes encoding the oxidative stress scavengers SOD2 and Catalase1. Chromatin immunoprecipitation assays confirm that, indeed, these genes are bonafide targets of KLF11. KLF11 expression renders cells more sensitive to oxidative drugs, an effect that is rescued by infection with recombinant adenoviruses expressing SOD2 and Catalasel. KLF11-regulated functions require the Mad1-like SID, indicating that these target genes involved in these phenomena are regulated via this corepressor system. These results demonstrate that SID-containing KLF repressor proteins can inhibit cell growth and neoplastic transformation, and outline for the first time cellular and molecular mechanisms by which these functions may be achieved.

Original languageEnglish (US)
Pages (from-to)4748-4758
Number of pages11
JournalEMBO Journal
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2003

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Sudden Infant Death
Cell growth
Genes
Repressor Proteins
Co-Repressor Proteins
Gene encoding
Oxidative stress
Transcription
Down-Regulation
Growth
Neoplastic Cell Transformation
Chromatin
Assays
Proteins
Chromatin Immunoprecipitation
Adenoviridae
Transgenic Mice
Oxidative Stress
Pharmaceutical Preparations
Infection

Keywords

  • Apoptosis
  • Cell growth
  • KLF11
  • mSin3A
  • SID

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation. / Fernandez-Zapico, Martin E; Mladek, Ann; Ellenrieder, Volker; Folch-Puy, Emma; Miller, Laurence J; Urrutia, Raul.

In: EMBO Journal, Vol. 22, No. 18, 15.09.2003, p. 4748-4758.

Research output: Contribution to journalArticle

Fernandez-Zapico, Martin E ; Mladek, Ann ; Ellenrieder, Volker ; Folch-Puy, Emma ; Miller, Laurence J ; Urrutia, Raul. / An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation. In: EMBO Journal. 2003 ; Vol. 22, No. 18. pp. 4748-4758.
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