کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3424087 1594260 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation
چکیده انگلیسی

All gammaherpsviruses encode at least one gene related to the cellular formylglycinamide ribonucleotide amidotransferase (FGARAT) enzyme but their biological roles are relatively unknown. The murine gammaherpesvirus 68 (MHV68) vFGARAT, ORF75c, mediates a proteasome-dependent degradation of the antiviral promyelocytic leukemia (PML) protein by an unknown mechanism, which is addressed in this study. We found that ORF75c interacts weakly with PML and SUMO-modified forms of PML are important for its degradation by ORF75c. ORF75c-mediated PML degradation was not dependent on two known cellular regulators of PML stability, Casein kinase II (CK2) and human papilloma virus E6-associated protein (E6AP). Finally, ORF75c had self-ubiquitination activity in vitro and its expression increased levels of ubiquitinated PML in transfected cells. Taken together, the evidence accumulated in this study provides new insights into the function of a vFGARAT and is consistent with a model in which ORF75c could mediate direct ubiquitination of PML resulting in its degradation by the proteasome.


► MHV68 ORF75c interacts weakly with PML and induces PML poly-ubiquitination in vivo.
► MHV68 ORF75c contains self-ubiquitination activity in vitro.
► PML regulators, CK2 and E6AP, are not required for ORF75c-induced PML degradation.
► SUMOylated PML is important for ORF75c-mediated PML degradation.
► MHV68 does not ubiquitously target SUMO-modified cellular proteins for degradation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 440, Issue 2, 5 June 2013, Pages 140–149
نویسندگان
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