STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling
| Autor: | Curt M. Horvath, Christina M. Ulane, Jason J. Rodriguez, Jean Patrick Parisien |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
STAT3 Transcription Factor
Immunology Apoptosis Mumps virus medicine.disease_cause Microbiology DDB1 Mice Viral Proteins Virology medicine Tumor Cells Cultured Animals Humans STAT1 Rubulavirus STAT2 STAT3 Cell Line Transformed biology Interleukin-6 Ubiquitin 3T3 Cells Interferon-beta Oncogenes biology.organism_classification Oncolytic virus Virus-Cell Interactions DNA-Binding Proteins Genes src STAT1 Transcription Factor Insect Science biology.protein Trans-Activators Cytokines Tyrosine kinase Signal Transduction |
| Zdroj: | Journal of virology. 77(11) |
| ISSN: | 0022-538X |
| Popis: | Mumps virus is a common infectious agent of humans, causing parotitis, meningitis, encephalitis, and orchitis. Like other paramyxoviruses in the genusRubulavirus, 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. |
| Databáze: | OpenAIRE |
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