NDLI: SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr)

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SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr)

Content Provider	Scilit
Author	Zhou, Xiaohong DeLucia, Maria Ahn, Jinwoo
Copyright Year	2016
Description	Journal: Journal of Biological Chemistry Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive biochemical activities of both endonucleases in DNA repair. Viral protein R (Vpr), a highly conserved accessory protein in primate lentiviruses, was previously reported to bind SLX4 to mediate down-regulation of MUS81. However, the detailed mechanism underlying MUS81 down-regulation is unclear. Here, we report that HIV-1 Vpr down-regulates both MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. Multiple Vpr variants, from HIV-1 and SIV, down-regulate both MUS81 and EME1. Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack $G_{2}$ arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced $G_{2}$ arrest is not correlated with MUS81-EME1 down-regulation. We also show that neither the interaction of MUS81-EME1 with Vpr nor their down-regulation is dependent on SLX4-SLX1. Together, these data provide new insight on a conserved function of Vpr in a host endonuclease down-regulation.
Related Links	http://www.jbc.org/content/291/33/16936.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016100/pdf http://www.jbc.org/article/S0021925820334396/pdf
Ending Page	16947
Page Count	12
Starting Page	16936
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m116.721183
Journal	Journal of Biological Chemistry
Issue Number	33
Volume Number	291
Language	English
Publisher	Elsevier BV
Publisher Date	2016-08-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology E3 Ubiquitin Ligase Western Blot Human Immunodeficiency Virus (hiv) Protein Degradation Viral Protein
Content Type	Text
Resource Type	Synopsis
Subject	Cell Biology Biochemistry Molecular Biology

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