MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner

被引:202
作者
Michels, AA
Nguyen, VT
Fraldi, A
Labas, V
Edwards, M
Bonnet, F
Lania, L
Bensaude, O
机构
[1] Ecole Normale Super, Lab Regulat Express Genet, CNRS, UMR 8541, F-75230 Paris 05, France
[2] Ecole Super Phys & Chim Ind Ville Paris, CNRS, UMR 7637, F-75005 Paris, France
[3] Univ Naples Federico II, Dipartimento Genet Biol Gen & Mol, I-80134 Naples, Italy
关键词
D O I
10.1128/MCB.23.14.4859-4869.2003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Positive transcription elongation factor b (P-TEFb) comprises a cyclin (T1 or T2) and a kinase, cyclin-dependent kinase 9 (CDK9), which phosphorylates the carboxyl-terminal domain of RNA polymerase II. P-TEFb is essential for transcriptional elongation in human cells. A highly specific interaction among cyclin T1, the viral protein Tat, and the transactivation response (TAR) element RNA determines the productive transcription of the human immunodeficiency virus genome. In growing HeLa cells, half of P-TEFb is kinase inactive and binds to the 7SK small nuclear RNA. We now report on a novel protein termed MAQ1 (for menage a quatre) that is also present in this complex. Since 7SK RNA is required for MAQ1 to associate with P-TEFb, a structural role for 7SK RNA is proposed. Inhibition of transcription results in the release of both MAQ1 and 7SK RNA from P-TEFb. Thus, MAQ1 cooperates with 7SK RNA to form a novel type of CDK inhibitor. According to yeast two-hybrid analysis and immunoprecipitations from extracts of transfected cells, MAQ1 binds directly to the N-terminal cyclin homology region of cyclins T1 and T2. Since Tat also binds to this cyclin T1 N-terminal domain and since the association between 7SK RNA/MAQ1 and P-TEFb competes with the binding of Tat to cyclin T1, we speculate that the TAR RNA/Tat lentivirus system has evolved to subvert the cellular 7SK RNA/MAQ1 system.
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页码:4859 / 4869
页数:11
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