HEXIM1 and the control of transcription elongation: from cancer and inflammation to AIDS and cardiac hypertrophy.
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is an inhibitor of positive transcription elongation factor b (P-TEFb) that has recently been shown to be involved in cancers, AIDS, cardiac hypertrophy and inflammation. It was first cloned from vascular smooth muscle cells (VSMCs) treated with hexamethylene bis-acetamide (HMBA), a compound that suppresses the proliferation of VSMCs. Little was kappanown about the biological function of HEXIM1 till the discovery of its association with P-TEFb. P-TEFb, a protein complex composed of cyclin-dependent kinase 9 and a cyclin partner, plays a key role in regulation of RNA polymerase II elongation. When associated with 7SK small nuclear RNA, HEXIM1 binds to P-TEFb and inhibits the kinase activity of P-TEFb. This finding provides the molecular basis for the inhibitory function of HEXIM1 in P-TEFb-dependent transcription, such as human immunodeficiency virus Tat transactivation and NFkappaB-mediated transcription. Recent evidences suggest an essential role of HEXIM1 in several diseases through transcriptional regulation.
Department of Cell Cycle Control, Institute of Molecular and Cell Biology, Singapore, Singapore.
Anwesha
A
Dey
Sheng-Hao
SH
Chao
David P
DP
Lane
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016601:RNA-Binding Proteins; D035602:Transcriptional Elongation Factors