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PMID: 16051811 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain.

Journal of virology ·Vol. 79 ·No. 16 ·2005-08-00 ·Pages 10180-9

Ulane CM, Kentsis A, Cruz CD, Parisien JP, Schneider KL, Horvath CM

Abstract

Transcription regulators STAT1 and STAT2 are key components of the interferon signaling system leading to innate antiviral immunity. The related STAT3 protein is a regulator of interleukin-6-type cytokine signals and can contribute to both cell growth and death important for cancer gene regulation and tumor survival. These three STAT proteins are targeted for proteasome-mediated degradation by RNA viruses in the Rubulavirus genus of the Paramyxoviridae. A single viral protein, the V protein, assembles STAT-specific ubiquitin ligase complexes from cellular components. Simian virus 5 (SV5) targets STAT1, human parainfluenza virus 2 targets STAT2, and mumps virus targets both STAT1 and STAT3. Analysis of the V-dependent degradation complex (VDC) composition and assembly revealed several features contributing to targeting specificity. SV5 and mumps V proteins require STAT2 to recruit the STAT1 target, yet mumps V protein binds STAT3 independent of STAT1 and STAT2. All Rubulavirus V proteins tested require cellular DDB1 to target STATs for degradation but differ in the use of Roc1, which is essential for mumps V STAT3 targeting. Protein interaction analysis reveals that paramyxovirus V proteins can homo- and heterooligomerize and that the conserved cysteine-rich zinc-binding C-terminal domain is necessary and sufficient for oligomerization. Purified SV5 V protein spontaneously assembles into spherical macromolecular particles, and similar particles constitute SV5 and mumps VDC preparations.

MeSH Terms
Carrier Proteins/physiology Cullin Proteins/physiology DNA-Binding Proteins/metabolism,physiology Dimerization STAT1 Transcription Factor STAT2 Transcription Factor STAT3 Transcription Factor Trans-Activators/metabolism Ubiquitin/metabolism Ubiquitin-Protein Ligases/chemistry Viral Proteins/chemistry,physiology
Chemicals
CUL4A protein, human Carrier Proteins Cullin Proteins DDB1 protein, human DNA-Binding Proteins RBX1 protein, human STAT1 Transcription Factor STAT2 Transcription Factor STAT3 Transcription Factor Trans-Activators Ubiquitin V protein, Paramyxovirus Viral Proteins Ubiquitin-Protein Ligases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ulane Christina M
Mount Sinai School of Medicine, New York, New York 10029, USA.
Kentsis Alex
Cruz Cristian D
Parisien Jean-Patrick
Schneider Kristi L
Horvath Curt M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.16.10180-10189.2005
Published
2005-08-00
Pages
10180-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1182666
Subset
IM
Grants
NIAID NIH HHS · R01 AI050707 · United States
NIAID NIH HHS · T32 AI007605 · United States
NIAID NIH HHS · 5T32AI07605-04 · United States
NIAID NIH HHS · AI50707 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.16.10180-10189.2005 PMC Full Text View journal details
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