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Int J Cancer. 2011 Apr 15;128(8):1836-42. doi: 10.1002/ijc.25524.

Role for transcription factor TFII-I in the suppression of SSeCKS/Gravin/Akap12 transcription by Src.

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  • 1Kinex Pharmaceuticals, LLC, Buffalo, NY, USA.

Abstract

The SSeCKS/Gravin/AKAP12 gene, encoding a kinase scaffolding protein with metastasis-suppressing activity, is transcriptionally downregulated in Src-transformed cells through the recruitment of HDAC1 to a Src-responsive proximal promoter site charged with Sp1, Sp3 and USF1. However, the ectopic expression of these proteins formed a suppressive complex in Src-transformed but not in parental NIH3T3 cells, suggesting the involvement of additional repressor factors. Transcription factor II-I (TFII-I) [general transcription factor 2i (Gtf2i)] was identified by mass spectrometry as being associated with the SSeCKS promoter complex in NIH3T3/Src cells, and moreover, the Src-induced tyrosine phosphorylation of TFII-I significantly increased its binding to the SSeCKS proximal promoter. siRNA-mediated knockdown of TFII-I or the expression of TFII-I(Y248/249F) caused the derepression of SSeCKS in NIH3T3/Src cells. Taken with previous data showing that the tyrosine phosphorylation of TFII-I facilitates its nuclear translocation, these data suggest that Src-family kinase-mediated phosphorylation converts a portion of TFII-I into a transcriptional repressor.

Copyright © 2010 UICC.

PMID:
20568114
[PubMed - indexed for MEDLINE]
PMCID:
PMC2997892
Free PMC Article

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