HBMG010 is a Novel Transcriptional Repressor Involved in TRAP1-Mediated Signal Transduction

초록

HBMG010 was initially identified as one of novel cDNAs expressed in mouse embryonic stem (ES) cells. HBMG010 encodes a basic protein (pI value of 9.97) composed of 468 amino acids. At both RNA and protein levels, HBMG010 is expressed mainly at cytoplasm in most of major adult tissue types and differentiating ES cells. GAL4-HBMG010 fusion protein-based luciferase reporter assay revealed that HBMG010 acts as a transcription repressor. To get more insights into the functional roles of HBMG010, we screened HBMG010-interacting protein genes from the human brain cDNA library by yeast two hybrid assay. One of five positive clones, tumor necrosis type I receptor associated protein (TRAP1)/hsp75, was confirmed its C-terminal domain interaction with HBMG010 in vivo. TRAP1 is a mitochondrial protein and likely to function in TNF-mediated NF-kB transcriptional regulation. In this study, we showed that TRAP1 inhibits transcriptional activation of the NF-kB dependent reporter and this repression effect is rescued by HBMG010. These results suggest that HBMG010 is a novel regulatory factor that is involved in TRAP1-mediated NF-kB repression.