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 (TGFß1), types I and II TGFß 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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ISBN | 9783639103359 |
---|---|
Sprache | ger |
Cover | Kartonierter Einband (Kt) |
Verlag | VDM Verlag Dr. Müller e.K. |
Jahr | 2008 |
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