PMID- 12504558
OWN - NLM
STAT- MEDLINE
DCOM- 20030508
LR  - 20190714
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 304
IP  - 2
DP  - 2002 Dec 20
TI  - Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes 
      from cellular components.
PG  - 160-6
AB  - Signal transducer and activator of transcription (STAT) proteins are normally 
      long-lived, but infection with certain Paramyxoviruses results in efficient loss 
      of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called 
      "V" is sufficient to mediate the destruction of STAT proteins. STAT degradation 
      is blocked by proteasome inhibitors, strongly implicating the ubiquitin 
      (Ub)-proteasome targeting system. We demonstrate that cellular expression of V 
      proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2) 
      induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins 
      catalyze Ub transfer in an ATP-dependent process that requires both Ub-activating 
      (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting 
      protein partners were isolated by affinity purification from human cells and 
      reveal a complex of associated cellular proteins. This complex includes both 
      STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a 
      protein related to a family of cellular Ub ligase complex subunits, cullin 4A 
      (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in 
      STAT1 degradation by SV5 infection were analyzed using small interfering RNAs. 
      These findings demonstrate the assembly of a V-dependent degradation complex that 
      includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on 
      SCF-type cellular E3 enzymes, we refer to this complex as VDC.
CI  - Copyright 2002 Elsevier Science (USA)
FAU - Ulane, Christina M
AU  - Ulane CM
AD  - Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, 
      USA.
FAU - Horvath, Curt M
AU  - Horvath CM
LA  - eng
GR  - AI-50707/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (DDB1 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT2 Transcription Factor)
RN  - 0 (STAT2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (V protein, Simian parainfluenza virus 5)
RN  - 0 (V protein, human parainfluenza virus type 1)
RN  - 0 (Viral Proteins)
RN  - 0 (Viral Structural Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Antigen-Antibody Complex/metabolism
MH  - Cells, Cultured
MH  - *Cullin Proteins
MH  - DNA-Binding Proteins/*metabolism
MH  - Humans
MH  - Ligases/*metabolism
MH  - Neoplasm Proteins/metabolism
MH  - RNA, Small Interfering/physiology
MH  - Respirovirus/*physiology
MH  - STAT1 Transcription Factor
MH  - STAT2 Transcription Factor
MH  - Trans-Activators/*metabolism
MH  - Ubiquitin-Protein Ligases
MH  - Viral Proteins/*physiology
MH  - Viral Structural Proteins/*physiology
EDAT- 2002/12/31 04:00
MHDA- 2003/05/09 05:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/05/09 05:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0042682202917733 [pii]
AID - 10.1006/viro.2002.1773 [doi]
PST - ppublish
SO  - Virology. 2002 Dec 20;304(2):160-6. doi: 10.1006/viro.2002.1773.