A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA

被引:1053
作者
Wei, P
Garber, ME
Fang, SM
Fischer, WH
Jones, KA
机构
[1] Salk Inst Biol Studies, Regulat Biol Lab, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Grad Program Biomed Sci, La Jolla, CA 92093 USA
关键词
D O I
10.1016/S0092-8674(00)80939-3
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
The HIV-1 Tat protein regulates transcription elongation through binding to the viral TAR RNA stem-loop structure. We have isolated a novel 87 kDa cyclin C-related protein (cyclin T) that interacts specifically with the transactivation domain of Tat. Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor. Remarkably, the interaction of Tat with cyclin T strongly enhances the affinity and specificity of the Tat:TAR RNA interaction, and confers a requirement for sequences in the loop of TAR that are not recognized by Tat alone. Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA.
引用
收藏
页码:451 / 462
页数:12
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