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 known 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 NFkB-mediated transcription. Recent evidences suggest an essential role of HEXIM1 in several diseases through transcriptional regulation.