PMID- 10082512
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 4
DP  - 1999 Apr
TI  - Structural and functional analysis of interferon regulatory factor 3:
      localization of the transactivation and autoinhibitory domains.
PG  - 2465-74
AB  - The interferon regulatory factor 3 (IRF-3) gene encodes a 55-kDa protein which is
      expressed constitutively in all tissues. In unstimulated cells, IRF-3 is present 
      in an inactive cytoplasmic form; following Sendai virus infection, IRF-3 is
      posttranslationally modified by protein phosphorylation at multiple serine and
      threonine residues located in the carboxy terminus. Virus-induced phosphorylation
      of IRF-3 leads to cytoplasmic to nuclear translocation of phosphorylated IRF-3,
      association with the transcriptional coactivator CBP/p300, and stimulation of DNA
      binding and transcriptional activities of virus-inducible genes. Using yeast and 
      mammalian one-hybrid analysis, we now demonstrate that an extended, atypical
      transactivation domain is located in the C terminus of IRF-3 between amino acids 
      (aa) 134 and 394. We also show that the C-terminal domain of IRF-3 located
      between aa 380 and 427 participates in the autoinhibition of IRF-3 activity via
      an intramolecular association with the N-terminal region between aa 98 and 240.
      After Sendai virus infection, an intermolecular association between IRF-3
      proteins is detected, demonstrating a virus-dependent formation of IRF-3
      homodimers; this interaction is also observed in the absence of virus infection
      with a constitutively activated form of IRF-3. Substitution of the C-terminal
      Ser-Thr phosphorylation sites with the phosphomimetic Asp in the region
      ISNSHPLSLTSDQ between amino acids 395 and 407 [IRF-3(5D)], but not the adjacent
      S385 and S386 residues, generates a constitutively activated DNA binding form of 
      IRF-3. In contrast, substitution of S385 and S386 with either Ala or Asp inhibits
      both DNA binding and transactivation activities of the IRF-3(5D) protein. These
      studies thus define the transactivation domain of IRF-3, two domains that
      participate in the autoinhibition of IRF-3 activity, and the regulatory
      phosphorylation sites controlling IRF-3 dimer formation, DNA binding activity,
      and association with the CBP/p300 coactivator.
FAU - Lin, R
AU  - Lin R
AD  - Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research,
      McGill University, Montreal, Canada H3T 1E2. mdli@musica.mcgill.ca
FAU - Mamane, Y
AU  - Mamane Y
FAU - Hiscott, J
AU  - Hiscott J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GAL4 protein, S cerevisiae)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
SB  - IM
MH  - Binding Sites
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/metabolism
MH  - DNA-Binding Proteins/*antagonists & inhibitors/*metabolism
MH  - Fungal Proteins/metabolism
MH  - Histone Acetyltransferases
MH  - Interferon Regulatory Factor-3
MH  - Models, Genetic
MH  - Nuclear Receptor Coactivator 3
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Processing, Post-Translational
MH  - Respirovirus/*metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Trans-Activators/metabolism
MH  - Transcription Factors/*antagonists & inhibitors/*metabolism
MH  - *Transcriptional Activation
PMC - PMC84039
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - 10.1128/mcb.19.4.2465 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Apr;19(4):2465-74. doi: 10.1128/mcb.19.4.2465.