HEXIM1 and the control of transcription elongation: from cancer and inflammation to AIDS and cardiac hypertrophy.

Abstract

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.

• Authors: Anwesha Dey, Sheng-Hao Chao, David P Lane
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 6 Issue 15 Pg. 1856-63 (Aug 01 2007) ISSN: 1551-4005 [Electronic] United States
• PMID: 17671421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• RNA-Binding Proteins
• Transcriptional Elongation Factors

Topics

• Acquired Immunodeficiency Syndrome (genetics, metabolism)
• Animals
• Cardiomegaly (metabolism)
• Humans
• Inflammation (genetics, metabolism)
• Neoplasms (metabolism)
• RNA-Binding Proteins (antagonists & inhibitors, metabolism)
• Transcriptional Elongation Factors (antagonists & inhibitors, metabolism)