PMID- 10080190
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 3
DP  - 1999 Mar
TI  - Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and
      cellular proliferation.
PG  - 326-9
AB  - c-Jun is a major component of the heterodimeric transcription factor AP-1 and is 
      essential for embryonic development, as fetuses lacking Jun die at mid-gestation 
      with impaired hepatogenesis and primary Jun-/- fibroblasts have a severe
      proliferation defect and undergo premature senescence in vitro. c-Jun and AP-1
      activities are regulated by c-Jun N-terminal phosphorylation (JNP) at serines 63 
      and 73 through Jun N-terminal kinases(JNKs). JNP is thought to be required for
      the anti-apoptotic function of c-Jun during hepatogenesis, as mice lacking the
      JNK kinase SEK1 exhibit liver defects similar to those seen in Jun-/- fetuses. To
      investigate the physiological relevance of JNP, we replaced endogenous Jun by a
      mutant Jun allele with serines 63 and 73 mutated to alanines (Jun(tm1wag);
      hereafter referred to as JunAA). Here we show that primary JunAA fibroblasts have
      proliferation- and stress-induced apoptotic defects, accompanied by reduced AP-1 
      activity. JunAA mice are viable and fertile, smaller than controls and resistant 
      to epileptic seizures and neuronal apoptosis induced by the excitatory amino acid
      kainate. Primary mutant neurons are also protected from apoptosis and exhibit
      unaltered JNK activity. Our results provide evidence that JNP is dispensable for 
      mouse development, and identify c-Jun as the essential substrate of JNK
      signalling during kainate-induced neuronal apoptosis.
FAU - Behrens, A
AU  - Behrens A
AD  - Research Institute of Molecular Pathology, Vienna, Austria.
FAU - Sibilia, M
AU  - Sibilia M
FAU - Wagner, E F
AU  - Wagner EF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (GABA Antagonists)
RN  - 0 (Mutagens)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 12H3O2UGSF (Methylnitronitrosoguanidine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Mitogen-Activated Protein Kinase 12)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SIV03811UC (Kainic Acid)
RN  - WM5Z385K7T (Pentylenetetrazole)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*genetics
MH  - Base Sequence
MH  - Cell Division/physiology
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Fibroblasts/drug effects/metabolism/radiation effects
MH  - GABA Antagonists/pharmacology
MH  - Gene Expression Regulation, Developmental/drug effects/radiation effects
MH  - Hippocampus/drug effects
MH  - Homozygote
MH  - Kainic Acid/pharmacology
MH  - Methylnitronitrosoguanidine/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Mutant Strains
MH  - Mitogen-Activated Protein Kinase 12
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - Mutagens/pharmacology
MH  - Mutation
MH  - Neurons/drug effects/pathology
MH  - Pentylenetetrazole/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-jun/*genetics/*metabolism
MH  - Seizures/chemically induced
MH  - Stress, Physiological/*genetics
MH  - Ultraviolet Rays
EDAT- 1999/03/18 03:02
MHDA- 2001/03/23 10:01
CRDT- 1999/03/18 03:02
PHST- 1999/03/18 03:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/18 03:02 [entrez]
AID - 10.1038/6854 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Mar;21(3):326-9. doi: 10.1038/6854.