SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication
AUTOR(ES)
Nevels, Michael
FONTE
American Society for Microbiology
RESUMO
The 72-kDa immediate-early 1 protein (IE1-72kDa) of human cytomegalovirus has been previously shown to be posttranslationally modified by covalent conjugation to the ubiquitin-related protein SUMO-1. Using an infectious bacterial artificial chromosome clone of human cytomegalovirus, we constructed a mutant virus (BADpmIE1-K450R) that is deficient for SUMOylation of IE1-72kDa due to a single amino acid exchange in the SUMO-1 attachment site. Compared to wild-type virus, this mutant grew more slowly and generated a reduced yield in infected human fibroblasts, indicating that SUMO modification is required for the full activity of IE1-72kDa. The lack of SUMOylation did not affect the intranuclear localization of IE1-72kDa, including its ability to target to and disrupt PML bodies and to bind to mitotic chromatin. Likewise, SUMOylation-deficient IE1-72kDa activated several viral promoters as efficiently as the wild-type protein. However, the failure to modify IE1-72kDa resulted in substantially reduced levels of the IE2 transcript and its 86-kDa protein (IE2-86kDa). These observations suggest that SUMO modification of IE1-72kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86kDa.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=434104Documentos Relacionados
- Phosphorylation of the Human Cytomegalovirus 86-Kilodalton Immediate-Early Protein IE2
- Human Cytomegalovirus 86-Kilodalton IE2 Protein Blocks Cell Cycle Progression in G1
- Identification of binding sites for the 86-kilodalton IE2 protein of human cytomegalovirus within an IE2-responsive viral early promoter.
- Functional interaction between the human cytomegalovirus 86-kilodalton IE2 protein and the cellular transcription factor CREB.
- Site-specific binding of the human cytomegalovirus IE2 86-kilodalton protein to an early gene promoter.