title: Degradation of polyomavirus JC T-antigen by stress involves the LIP isoform of C/EBP.
abstract: Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum. CCAAT/enhancer binding proteins are one of the cellular proteins whose expression is upregulated during ER stress. Previously, we have identified C/EBPbeta isoforms, especially LIP, as a negative regulator of polyomavirus JC (JCV), the causative agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). Here, we show that the induction of ER stress by thapsigargin increase the expression of endogenous LIP and the degradation of JCV T-antigen in a JCV-transgenic mouse tumor cell line. Our results also revealed that overexpression of LIP significantly reduced the level of T-Ag and this effect is reversed upon siRNA-mediated silencing of LIP. Immunoprecipitation/Western blot experiments indicated that LIP interacts with T-antigen directly. Treatment of cells that overexpress LIP with MG115, a proteasome inhibitor, partially rescued LIP-mediated degradation of T-antigen. Our observations point to a role of LIP in ER stress regulation of T-antigen stability and may open a new avenue to study host-virus interaction during ER stress.
authors.affiliation: a Department of Neuroscience; Center for Neurovirology; Temple University School of Medicine ; Philadelphia , PA USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bellizzi
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.forename: Hassen S
authors.initials: HS
authors.lastname: Wollebo
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D007577:JC Virus / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D013251:Steroid Isomerases / Q000276:immunology / Q000378:metabolism*
chemical_list: D000957:Antigens, Viral, Tumor; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; C545013:Cebpb protein, mouse; D020033:Protein Isoforms; C490380:Ebp protein, mouse; D013251:Steroid Isomerases
keywords: CAAT/enhancer binding protein-beta; endoplasmic reticulum stress; large transforming antigen; liver-inhibitory isoform; polyomavirus JC