PMID- 22184250
OWN - NLM
STAT- MEDLINE
DCOM- 20120306
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 1
DP  - 2012 Jan 3
TI  - Site-specific ubiquitination is required for relieving the transcription factor 
      Miz1-mediated suppression on TNF-alpha-induced JNK activation and inflammation.
PG  - 191-6
LID - 10.1073/pnas.1105176108 [doi]
AB  - The transcription factor zinc-finger protein Miz1 represses TNF-alpha-induced JNK 
      activation and the repression is relieved upon TNF-alpha stimulation. However, the 
      underlying mechanism is incompletely understood. Here we report that Miz1 
      interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the 
      RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the 
      ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-alpha-induced JNK 
      activation. Upon TNF-alpha stimulation, Miz1 rapidly undergoes K48-linked 
      polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal 
      degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 
      by arginines generates a nondegradable Miz1 mutant, which significantly 
      suppresses TNF-alpha-induced JNK1 activation and inflammation. Thus, our results 
      reveal a molecular mechanism by which the repression of TNF-alpha-induced JNK 
      activation by Miz1 is de-repressed by its own site-specific ubiquitination and 
      degradation, which may account for the temporal control of TNF-alpha-JNK signaling.
FAU - Liu, Jing
AU  - Liu J
AD  - Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, 
      USA.
FAU - Yan, Jie
AU  - Yan J
FAU - Jiang, Shan
AU  - Jiang S
FAU - Wen, Jing
AU  - Wen J
FAU - Chen, Long
AU  - Chen L
FAU - Zhao, Yingming
AU  - Zhao Y
FAU - Lin, Anning
AU  - Lin A
LA  - eng
GR  - R01 CA100460/CA/NCI NIH HHS/United States
GR  - GM081603/GM/NIGMS NIH HHS/United States
GR  - CA100460/CA/NCI NIH HHS/United States
GR  - R01 GM081603/GM/NIGMS NIH HHS/United States
GR  - ES015868/ES/NIEHS NIH HHS/United States
GR  - R01 ES015868/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111219
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Inflammation Mediators)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Inhibitors of Activated STAT)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (ZBTB17 protein, human)
RN  - 120904-94-1 (Polyubiquitin)
RN  - EC 2.3.2.27 (Miz1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Inflammation/*enzymology/genetics/pathology
MH  - Inflammation Mediators/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Kruppel-Like Transcription Factors/deficiency/*metabolism
MH  - Lysine/metabolism
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Models, Biological
MH  - Nuclear Proteins/deficiency/*metabolism
MH  - Polyubiquitin/metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Inhibitors of Activated STAT/deficiency/*metabolism
MH  - Proteolysis/drug effects
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Ubiquitination/*drug effects
PMC - PMC3252938
COIS- The authors declare no conflict of interest.
EDAT- 2011/12/21 06:00
MHDA- 2012/03/07 06:00
PMCR- 2012/07/03
CRDT- 2011/12/21 06:00
PHST- 2011/12/21 06:00 [entrez]
PHST- 2011/12/21 06:00 [pubmed]
PHST- 2012/03/07 06:00 [medline]
PHST- 2012/07/03 00:00 [pmc-release]
AID - 1105176108 [pii]
AID - 201105176 [pii]
AID - 10.1073/pnas.1105176108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):191-6. doi: 10.1073/pnas.1105176108. 
      Epub 2011 Dec 19.