TRIM28 promotes HIV-1 latency by SUMOylating CDK9 and inhibiting P-TEFb.

Abstract:

:Comprehensively elucidating the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) latency is a priority to achieve a functional cure. As current 'shock' agents failed to efficiently reactivate the latent reservoir, it is important to discover new targets for developing more efficient latency-reversing agents (LRAs). Here, we found that TRIM28 potently suppresses HIV-1 expression by utilizing both SUMO E3 ligase activity and epigenetic adaptor function. Through global site-specific SUMO-MS study and serial SUMOylation assays, we identified that P-TEFb catalytic subunit CDK9 is significantly SUMOylated by TRIM28 with SUMO4. The Lys44, Lys56 and Lys68 residues on CDK9 are SUMOylated by TRIM28, which inhibits CDK9 kinase activity or prevents P-TEFb assembly by directly blocking the interaction between CDK9 and Cyclin T1, subsequently inhibits viral transcription and contributes to HIV-1 latency. The manipulation of TRIM28 and its consequent SUMOylation pathway could be the target for developing LRAs.

journal_name

Elife

journal_title

eLife

authors

Ma X,Yang T,Luo Y,Wu L,Jiang Y,Song Z,Pan T,Liu B,Liu G,Liu J,Yu F,He Z,Zhang W,Yang J,Liang L,Guan Y,Zhang X,Li L,Cai W,Tang X,Gao S,Deng K,Zhang H

doi

10.7554/eLife.42426

subject

Has Abstract

pub_date

2019-01-17 00:00:00

issn

2050-084X

pii

42426

journal_volume

8

pub_type

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