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Regulation of the Krüppel-like Factor 6 Tumor Suppressor: Ras Promotes Cancer Cell Growth Via Alternative Splicing-mediated Inactivation of Klf6
Steven Yea
Regulation of the Krüppel-like Factor 6 Tumor Suppressor: Ras Promotes Cancer Cell Growth Via Alternative Splicing-mediated Inactivation of Klf6
Steven Yea
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 (TGF¿1), types I and II TGF¿ 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.
Medios de comunicación | Libros Paperback Book (Libro con tapa blanda y lomo encolado) |
Publicado | 6 de noviembre de 2008 |
ISBN13 | 9783639103359 |
Editores | VDM Verlag Dr. Müller |
Páginas | 168 |
Dimensiones | 231 g |
Lengua | English |
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