Role of the HIV-1 positive elongation factor P-TEFb and inhibitors thereof.
Transcription is considered to be a crucial step in the replication cycle of HIV-1. Tat regulates an early step of transcription elongation. The positive elongation factor P-TEFb, a heterodimer containing a catalytic subunit (CDK9) and unique regulatory cyclins (CycT1), is required for HIV-1 Tat transcriptional activation. This is a potential target for new HIV-1 transcription inhibitors. Without P-TEFb, transactivation is restrained and only short transcripts are generated. All the P-TEFb inhibitors can suppress the HIV-1 transactivation process by inhibition of CycT1, CDK9 or their interaction. Several low-molecular-weight compounds such as flavopiridol, roscovitine and the human small nuclear RNA 7SK which have been showed to possess potent anti-HIV activity by interfering with P-TEFb functions are reviewed in this article.
Wang
Yan
Y
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No.44 Wenhuaxi Road, Jinan 250012 , China.
Liu
Xin-Yong
XY
De Clercq
Erik
E
D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D042925:Positive Transcriptional Elongation Factor B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000737:chemistry / Q000494:pharmacology; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000494:pharmacology; D000077546:Roscovitine; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D005419:Flavonoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D012342:RNA, Small Nuclear; D000077546:Roscovitine; C077990:alvocidib; D042925:Positive Transcriptional Elongation Factor B