Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The positive transcription elongation factor b (P-TEFb) is a heterodimeric complex composed of cyclin-dependent kinase 9 and its regulator cyclin T1/2. It stimulates transcription elongation by phosphorylation of serine 2 residues in the carboxy-terminal domain of polymerase II. 7SK RNA and HEXIM proteins can antagonize transcriptional stimulation by sequestering P-TEFb in a catalytically inactive ribonucleoprotein (RNP). Here, we show that the previously uncharacterized La-related protein 7 (LARP7) has a role in 7SK-mediated regulation of transcription. LARP7 binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA and is an integral part of the 7SK RNP. On stimulation, LARP7 remains associated with 7SK RNA, whereas P-TEFb is released. Interestingly, reduction of LARP7 by RNA interference enhances transcription from cellular polymerase II promoters, as well as a TAT-dependent HIV-1 promoter. Thus, LARP7 is a negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system.
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PMID:The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes. 1848 87

A variety of cellular factors participates in the HIV-1 life cycle. Among them is the well characterized cyclin T1 (CYCT1). CycT1 binds to cyclin-dependent kinase 9 (CDK9) and forms the positive transcription elongation factor-b (P-TEFb). P-TEFb is then recruited by HIV-1 TAT to the HIV-1 long terminal repeat (LTR) promoter and subsequently leads to phosphorylation of the C-terminal domain of RNA polymerase II (pol II), enhanced processivity of pol II, and transcription of a full-length HIV-1 RNA. In this study, we report the identification of a new CYCT1 splice variant, designated as CYCT1b, and accordingly we renamed CYCT1 as CYCT1a. CYCT1b was detected in several cell lines, including primary human CD4 T cells, and its expression was subject to cell cycle regulation. Similar to CYCT1a, CYCT1b was primarily localized in the nucleus. CYCT1b expression was found to be inversely correlated with HIV-1 gene expression and replication. This inverse correlation appeared to involve TAT transactivation, CDK9 binding, and subsequent recruitment of P-TEFb to the HIV-1 LTR promoter and pol II C-terminal domain phosphorylation. In agreement with these findings, CYCT1b expression led to direct inhibition of TAT-transactivated transcription of the HIV-1 LTR promoter. Taken together, these results show that the newly identified CYCT1b splice variant inhibits HIV-1 transcription and may provide new clues for the development of anti-HIV strategies.
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PMID:Inhibition of HIV-1 transcription and replication by a newly identified cyclin T1 splice variant. 2356 10