Human cytomegalovirus protein pp71 induces Daxx SUMOylation.
Proteins that participate in a diverse array of cellular processes can be modified covalently and reversibly on lysine residues by the small ubiquitin-like modifier proteins termed SUMOs. In some instances, such modification profoundly affects protein function, but the biological significance of many SUMOylation events remains unknown. Protein SUMOylation is modulated during many viral infections. Here we demonstrate that the human cytomegalovirus (HCMV) pp71 protein promotes the SUMOylation of its cellular substrate, Daxx. A component of promyelocytic leukemia nuclear bodies, Daxx is a transcriptional corepressor that silences the expression of viral immediate-early (IE) genes at the start of both lytic and quiescent HCMV infections. pp71 is a tegument component delivered directly to cells by infecting HCMV virions. At the start of lytic infections, it travels to the nucleus and stimulates viral IE gene expression by displacing the chromatin remodeling protein ATRX from Daxx and by mediating Daxx degradation through a rare ubiquitin-independent, proteasome-dependent process. Here we report that pp71 also substantially increases the basal level of SUMOylated Daxx observed in cells. To date, consequences of Daxx SUMOylation have not been observed for cellular promoters, and we detected no qualitative change in viral IE gene expression in the absence of pp71-induced Daxx SUMOylation. Thus, while pp71 enhances the basal level of SUMOylated Daxx, the role that this modification plays in regulating Daxx activity in uninfected or HCMV-infected cells remains an enigma.
Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
Jiwon
J
Hwang
Robert F
RF
Kalejta
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D056970:Co-Repressor Proteins; D003587:Cytomegalovirus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014764:Viral Proteins; C051298:cytomegalovirus phosphoprotein 71kDa