HBMG010 is a Universal HDAC1-dependent Transcription Repressor that Inhibits MAT1-mediated Transcriptional Activity of the CAK complex (cyclinH-cdk7-MAT1)

초록

HBMG010 was initially identified as one of novel cDNAs expressed in mouse embryonic stem (ES) cells. It encodes a basic polypeptide (pI value of 9.97) of 468 amino acids and containing a prominent coiled-coil domain in the central region of the protein. HBMG010 expresses in most of the major adult tissues and differentiating ES cells, and exists largely in cytoplasm. Over-expression of the HBMG010 protein inhibits the rate of cell proliferation. To understand the HBMG010-mediated cell proliferation regulation, a GAL4-HBMG010 fusion protein-based luciferase reporter assay was performed. As a result, it was revealed that HBMG010 acts as a general transcriptional repressor and this repression was augmented by HDAC1. Indeed, the protein-protein interaction between HBMG010 and HDAC1 was confirmed. To identify other HBMG010-interacting protein genes, we screened the human brain cDNA library using a yeast two-hybrid assay. At the end, we identified MAT1, as one of HBMG010 interacting clones. As an assembly factor of CAK complex (cyclinH-cdk7-MAT1) that is a subunit of general transcription factor TFIIH, MAT1 modulates CAK subunit specificity and deregulation of CAK function during cell cycle progression. We found that the coiled-coil region of HBMG010 interacts with the XPD and XPB binding coiled-coil domain of MAT1. Furthermore, MAT1 rescued the transcriptional activity of reporter gene that was repressed by GAL4-HBMG010, increasing cell proliferation rate. These results suggest that HBMG010 is a novel transcriptional co-repressor for MAT1-mediated cell cycle progression and it acts synergistically with HDAC1 by direct protein-protein interaction.