KLF8 recruits the p300 and PCAF co-activators to its amino terminal activation domain to activate transcription.

ABSTRACT: Krüppel-like factor 8 (KLF8) regulates critical cellular processes including cell cycle progression, transformation, epithelial-to-mesenchymal transition, migration and invasion by either repressing or activating target gene promoters. As a repressor, KLF8 recruits the CtBP co-repressor via its PVDLS repression motif. However, how KLF8 acts as an activator has not been determined. Here we report the identification of both the KLF8 activation domain and associated co-activators. By site-directed mutagenesis and cyclin D1 promoter reporter assays using both mouse fibroblasts and human epithelial cells, we determined that deletion of residues 100-260 or mutation of Q118-Q248 abolished KLF8 transactivity. this transactivity was dramatically reduced in p300(-/-), CBP(-/-) or PCAF(-/-) cells and

SUBMITTER: Urvalek AM 

PROVIDER: S-EPMC2888133 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature