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

Christina M. Ulane, Jason J. Rodriguez, Jean Patrick Parisien, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6385-6393
Number of pages9
JournalJournal of virology
Volume77
Issue number11
DOIs
StatePublished - Jun 2003

ASJC Scopus subject areas

  • Insect Science
  • Virology
  • Microbiology
  • Immunology

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