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PMID: 12743296 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling.

Journal of virology ·Vol. 77 ·No. 11 ·2003-06-00 ·Pages 6385-93

Ulane CM, Rodriguez JJ, Parisien JP, Horvath CM

Abstract

Mumps virus is a common infectious agent of humans, causing parotitis, meningitis, encephalitis, and orchitis. Like other paramyxoviruses in the genus Rubulavirus, mumps virus catalyzes the proteasomal degradation of cellular STAT1 protein, a means for escaping antiviral responses initiated by alpha/beta and gamma interferons. We demonstrate that mumps virus also eliminates cellular STAT3, a protein that mediates transcriptional responses to cytokines, growth factors, nonreceptor tyrosine kinases, and a variety of oncogenic stimuli. STAT1 and STAT3 are independently targeted by a single mumps virus protein, called V, that assembles STAT-directed ubiquitylation complexes from cellular components, including STAT1, STAT2, STAT3, DDB1, and Cullin4A. Consequently, mumps virus V protein prevents responses to interleukin-6 and v-Src signals and can induce apoptosis in STAT3-dependent multiple myeloma cells and transformed murine fibroblasts. These findings demonstrate a unique cytokine and oncogene evasion property of mumps virus that provides a molecular basis for its observed oncolytic properties.

MeSH Terms
3T3 Cells Animals Apoptosis Cell Line, Transformed Cytokines/metabolism DNA-Binding Proteins/metabolism Genes, src/physiology Humans Interferon-beta/metabolism Interleukin-6/metabolism Mice Mumps virus/pathogenicity,physiology Oncogenes/physiology STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Trans-Activators/metabolism Tumor Cells, Cultured Ubiquitin/metabolism Viral Proteins/metabolism
Chemicals
Cytokines DNA-Binding Proteins Interleukin-6 STAT1 Transcription Factor STAT1 protein, human STAT3 Transcription Factor STAT3 protein, human Stat1 protein, mouse Stat3 protein, mouse Trans-Activators Ubiquitin Viral Proteins Interferon-beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ulane Christina M
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Rodriguez Jason J
Parisien Jean-Patrick
Horvath Curt M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.11.6385-6393.2003
Published
2003-06-00
Pages
6385-93
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC155014
Subset
IM
Grants
NIAID NIH HHS · R01 AI048722 · United States
NIAID NIH HHS · AI-50707 · United States
NIGMS NIH HHS · T32 GM062754 · United States
NIAID NIH HHS · AI-48722 · United States
NIAID NIH HHS · R21 AI048722 · United States
NIAID NIH HHS · R01 AI050707 · United States
External Links
PubMed source DOI: 10.1128/jvi.77.11.6385-6393.2003 PMC Full Text View journal details
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