TRIM5α is a SUMO substrate

Retrovirology

Sébastien Nisole²  Uriel Hazan¹  Nathalie J Arhel³  Débora M Portilho³  Jacques Dutrieux² 

[1] LBPA, CNRS UMR 8113, Ecole Normale Supérieure de Cachan, Cachan, 94235, France;INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints-Pères, Paris, 75006, France;INSERM U941, University Institute of Hematology, Saint-Louis Hospital, Paris, 75010, France

关键词: HIV-1;    Restriction factor;    SUMO;    TRIM5α;   

Others  :  1174974
DOI  :  10.1186/s12977-015-0155-7

 received in 2014-12-16, accepted in 2015-03-02,  发布年份 2015

【 摘 要 】

Background

The TRIM5α restriction factor interferes with retroviral infections by inhibiting an early step of viral replication. TRIM5α activity was recently proposed to be regulated by the SUMO machinery and one SUMO consensus conjugation site as well as three putative SUMO interacting motifs (SIMs) were identified within TRIM5α sequence. Whereas mutation of the SIM sequences was found to abolish TRIM5α antiviral activity, mutation of the consensus SUMO conjugation site did not affect its restriction capacity, although this putative site has never been shown to be actually a SUMO substrate.

Findings

Here we further demonstrate that TRIM5α relies on the SUMO machinery to promote restriction, since SUMO1 overexpression enhances TRIM5α-mediated retroviral inhibition whereas knockdown of SUMO1 or E2 SUMO conjugating enzyme Ubc9 prevents restriction. Furthermore, we show for the first time that TRIM5α is SUMOylated both in vitro and in cellulo and that Lysine 10 is the main SUMOylation site. Mutation of the consensus SUMO conjugation motif in position 10 abrogated SUMOylation at this position, but did not disrupt TRIM5α antiviral activity.

Conclusions

Altogether, our results confirm that the SUMO machinery is involved in TRIM5α-mediated retroviral restriction, and demonstrate that TRIM5α is a SUMO 1 and SUMO 2 substrate. The inability to abrogate TRIM5α antiviral activity by mutating its main SUMO conjugation motif supports the notion that non-covalent interaction with SUMO or SUMOylated proteins rather than TRIM5α direct SUMOylation is required.

【 授权许可】

   
2015 Dutrieux et al.; licensee BioMed Central.

【 图 表 】

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