http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G
( David J Stanley ),( Koen Bartholomeeusen ),( David C Crosby ),( Dong Yong Kim ),( Eunju Kwon ),( Linda Yen ),( Nathalie Caretta Cartazo ),( Ming Li ),( Stefanie J?ger ),( Jeremy Mason Herr ),( Fumia 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV). HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellularrestriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G). Pharmacological inhibition of the NEDD8 E1 by MLN4924 or knockdown of either UBE2F or its RING-protein binding partner RBX2 bypasses the effect of Vif, restoring the restriction of HIV by A3G. NMR mapping and mutational analyses define specificity determinants of the UBE2F NEDD8 cascade. These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.
CBFβ Stabilizes HIV Vif to Counteract APOBEC3 at the Expense of RUNX1 Targen Gene Expression
( Dong Young Kim ),( Eunju Kwon ),( Paul D Hartley ),( David C Crosby ),( Sumanjit Mann ),( Nevan J Krogan ),( John D Gross ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
The HIV-1 accessory protein Vif hijacks a cellular Cullin-RING ubiquitin ligase, CRL5, to promote degradation of the APOBEC3 (A3) family of restriction factors. Recently, the cellular transcription cofactor CBFβ was shown to form a complex with CRL5-Vif and to be essential for A3 degradation and viral infectivity. We now demonstrate that CBFβ is required for assembling a well-ordered CRL5-Vif complex by inhibiting Vifoligomerization and by activating CRL5-Vif via direct interaction. The CRL5-Vif-CBFβ holoenzyme forms a well-defined heterohexamer, indicating that Vif simultaneously hijacks CRL5 and CBFβ. Heterodimers of CBFβ and RUNX transcription factors contribute toward the regulation of genes, including those with immune system functions. We show that binding of Vif to CBFβ is mutually exclusive with RUNX heterodimerization and impacts the expression of genes whose regulatory domains are associated with RUNX1. Our results provide a mechanism by which a pathogen with limited coding capacity uses one factor to hijack multiple host pathways.