P-TEFb as A Promising Therapeutic Target.

Abstract

The positive transcription elongation factor b (P-TEFb) was first identified as a general factor that stimulates transcription elongation by RNA polymerase II (RNAPII), but soon afterwards it turned out to be an essential cellular co-factor of human immunodeficiency virus (HIV) transcription mediated by viral Tat proteins. Studies on the mechanisms of Tat-dependent HIV transcription have led to radical advances in our knowledge regarding the mechanism of eukaryotic transcription, including the discoveries that P-TEFb-mediated elongation control of cellular transcription is a main regulatory step of gene expression in eukaryotes, and deregulation of P-TEFb activity plays critical roles in many human diseases and conditions in addition to HIV/AIDS. P-TEFb is now recognized as an attractive and promising therapeutic target for inflammation/autoimmune diseases, cardiac hypertrophy, cancer, infectious diseases, etc. In this review article, I will summarize our knowledge about basic P-TEFb functions, the regulatory mechanism of P-TEFb-dependent transcription, P-TEFb's involvement in biological processes and diseases, and current approaches to manipulating P-TEFb functions for the treatment of these diseases.

• Authors: Koh Fujinaga
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 4 (Feb 14 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 32075058 (Publication Type: Journal Article, Review)

Chemical References

• tat Gene Products, Human Immunodeficiency Virus
• Positive Transcriptional Elongation Factor B

Topics

• Gene Expression Regulation, Viral (drug effects)
• HIV Infections (drug therapy, genetics, virology)
• HIV-1 (genetics, pathogenicity)
• Humans
• Positive Transcriptional Elongation Factor B (antagonists & inhibitors, genetics)
• Transcription, Genetic (drug effects)
• tat Gene Products, Human Immunodeficiency Virus (genetics)