Functional characterization of a human cyclin T1 mutant reveals a different binding surface for Tat and HEXIM1

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• 作者：Alona Kuzmina^a ; Uzi Hadad^b ; Koh Fujinaga^c ; Ran Taube^a ; ^{rantaube@bgu.ac.il}
• 关键词：HIV ; Positive transcription elongation factor b (P-TEFb) ; Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) ; Cyclin T1 ; Cdk9 ; Tat
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：10 May, 2012
• 卷：426
• 期：2
• 页码：152-161
• 文件大小：857 K

摘要

HIV transcription is regulated at the step of elongation by the viral Tat protein and the cellular positive transcription elongation factor b (P-TEFb; Cdk9/cyclin T1). Herein, a human cyclin T1 mutant, cyclin T1-U7, which contains four substitutions and one deletion in the N-terminal cyclin box, was stably expressed in HeLa cells. HIV transcription was efficiently inhibited in HeLa-HA-CycT1-U7 stable cells. Cyclin T1-U7 bound Tat but did not modulate its expression levels, which remained high. Importantly cyclin T1-U7 failed to interact with Cdk9 or HEXIM1 and did not interfere with endogenous P-TEFb activity to stimulate MEF2C or NFkB mediated transcription. In a T cell line and primary CD4+ cells, cyclin T1-U7 also inhibited HIV transcription. We conclude that cyclin T1-U7 sequesters Tat from P-TEFb and inhibits HIV transcription. Importantly, N-terminal residues in cyclin T1 are specifically involved in the binding of cyclin T1 to HEXIM1 but not to Tat.