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

✍ Scribed by Yahao Bu; Lingqiu Gao; Irwin H. Gelman

• Book ID: 102275661
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 332 KB
• Volume: 128
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.25524

✦ Synopsis

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.