title: Host cell sumoylation level influences papillomavirus E2 protein stability.
abstract: The stability of papillomavirus E2 proteins is regulated by proteasomal degradation, and regulation of degradation could contribute to the higher expression levels of E2 proteins observed in suprabasal layers of differentiated skin. We have recently shown that the E2 proteins are modified by sumoylation [Wu Y-C, Roark AA, Bian X-L, Wilson, VG (2008) Virol 378:329-338], and that sumoylation levels are up-regulated during keratinocyte differentiation [Deyrieux AF, Rosas-Acosta G, Ozbun MA, Wilson VG (2007) J Cell Sci 120:125-136]. These observations, coupled with the known ability of sumoylation to prevent proteasomal degradation of certain proteins, suggested that this modification might contribute to stabilizing E2 proteins in suprabasal keratinocytes. Conditions that increased overall sumoylation were found to increase the intracellular amounts of the HPV11, 16, and 18 E2 proteins. No effect of sumoylation was seen on E2 transcripts, and the increased levels of E2 proteins resulted from a greatly increased half-life for the E2 proteins. In vitro studies confirmed that sumoylation could block the proteasomal degradation of the 16E2 protein. Interestingly, this stabilization effect was indirect as it did not require sumoylation of 16E2 itself and must be acting through sumoylation of a cellular target(s). This sumoylation-dependent, indirect stabilization of E2 proteins is a novel process that may couple E2 levels to changes in the cellular environment. Specifically, our results suggest that the levels of papillomavirus E2 protein could be up-regulated in differentiating keratinocytes in response to the increased overall sumoylation that accompanies differentiation.
authors.affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, Reynolds Medical Building, College Station, TX 77843-1114, USA.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Wu
authors.forename: Xue-Lin
authors.initials: XL
authors.lastname: Bian
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Heaton
authors.forename: Adeline F
authors.initials: AF
authors.lastname: Deyrieux
authors.forename: Van G
authors.initials: VG
authors.lastname: Wilson
mesh_terms: D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D025842:SUMO-1 Protein / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex