HBMG010 is a Universal HDAC1-dependent Transcription Co-repressor that Inhibits MAT1-mediated Transcriptional Activity

초록

HBMG010 was initially identified as one of novel cDNAs expressed in mouse embryonic stem (ES) cells. It encodes a basic polypeptide of 468 amino acids. HBMG010 expresses in most of the major adult tissues and differentiating ES cells, and exists largely in cytoplasm. Antisense expression of HBMG010 suppressed transcriptional activities of genes that were chosen randomly. Furthermore, over-expression of the HBMG010 protein reduced the rate of cell proliferation. To understand the HBMG010-mediated regulation of gene expression and cell proliferation, a GAL4-HBMG010 fusion protein-based reporter assay was performed. Indeed, overexpression of HBMG010 repressed all reporter genes tested and this repression activity was intensified by HDAC1. MAT1, an assembly factor of CAK complex (cyclinH-cdk7-MAT1) that is a subunit of general transcription factor TFIIH, modulates CAK subunit specificity and CAK function in the regulation of cell cycle G(1) exit, and identified as one of HBMG010 interacting clones by screening the human brain cDNA library, rescued the transcriptional repression activity mediated by HBMG010 and increased cell proliferation rate. These results suggest that HBMG010 is a novel transcriptional co-repressor for MAT1-mediated cell cycle progression.