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Regulation of the Krüppel-like Factor 6 Tumor Suppressor

Regulation of the Krüppel-like Factor 6 Tumor Suppressor

Scott L. Friedman / Steven Yea

83,92 €
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Editorial:
KS OmniScriptum Publishing
Año de edición:
2008
Materia
Medicina: cuestiones generales
ISBN:
9783639103359
83,92 €
IVA incluido
Disponible

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KLF6 is a ubiquitously expressed Krüppel-like transcription factor whose role in vitro and in vivo role has not been fully identified. Like other members of the Krüppel-like family, KLF6 contains a conserved C-terminal three zinc finger DNA-binding domain (C2H2 motifs) and a unique N-terminal transactivation domain. KLF6 directly binds DNA at GC box promoter elements. Transcriptional targets of KLF6 include collagen 1, transforming growth factor beta 1 (TGFβ1), types I and II TGFβ receptors, urokinase type plasminogen activator (uPA), and the human immunodeficiency virus long terminal repeat (HIV-1 LTR). Here, we identify a novel mechanism of carcinogenesis, whereby oncogenic Ras signaling enhances alternative splicing-mediated inactivation of the KLF6 tumor suppressor in hepatocellular carcinomas. These Ras-dependent splice forms are shown to abrogate KLF6-mediated growth suppression, and ectopic KLF6 splice variant expression can restore a Ras-transformed phenotype.

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