标题: CUL5-Mediated APOBEC3G Degradation in HIV Infection [打印本页] 作者: wwwkkk83 时间: 2019-7-24 13:34 标题: CUL5-Mediated APOBEC3G Degradation in HIV Infection ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection
Ruth Hüttenhain
Jiewei Xu
Lily A. Burton
David E. Gordon
Judd F. Hultquist
Jeffrey R. Johnson
Laura Satkamp
Joseph Hiatt
David Y. Rhee
Kheewoong Baek
David C. Crosby
Alan D. Frankel
Alexander Marson
J. Wade Harper
Arno F. Alpi
Brenda A. Schulman
John D. Gross
Nevan J. Krogan 14
Summary
The Cullin-RING E3 ligase (CRL) family is commonly hijacked by pathogens to redirect the host ubiquitin proteasome machinery to specific targets. During HIV infection, CRL5 is hijacked by HIV Vif to target viral restriction factors of the APOBEC3 family for ubiquitination and degradation. Here, using a quantitative proteomics approach, we identify the E3 ligase ARIH2 as a regulator of CRL5-mediated APOBEC3 degradation. The CUL5 Vif/CBFß complex recruits ARIH2 where it acts to transfer ubiquitin directly to the APOBEC3 targets. ARIH2 is essential for CRL5-dependent HIV infectivity in primary CD4 + T cells. Furthermore, we show that ARIH2 cooperates with CRL5 to prime other cellular substrates for polyubiquitination, suggesting this may represent a general mechanism beyond HIV infection and APOBEC3 degradation. Taken together, these data identify ARIH2 as a co-factor in the Vif-hijacked CRL5 complex that contributes to HIV infectivity and demonstrate the operation of the E1-E2-E3/E3-substrate ubiquitination mechanism in a viral infection context.