PMID- 10617104
OWN - NLM
STAT- MEDLINE
DCOM- 20000118
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 74
IP  - 1
DP  - 2000 Jan
TI  - Changes of the trans-activating potential of AP-1 transcription factor during
      cyclosporin A-induced apoptosis of glioma cells are mediated by phosphorylation
      and alterations of AP-1 composition.
PG  - 42-51
AB  - Although the AP-1 transcription factor is known to play a role in cell
      proliferation and activation, it is also involved in apoptosis of cells in
      response to stress, DNA-damaging agents, or lack of survival signals. To
      understand how AP-1 might contribute to distinct biological processes, we tested 
      a hypothesis that changes in AP-1 composition or phosphorylation state modulate
      its transcriptional activity during cyclosporin A-induced apoptosis of glioma
      cells. The induction of AP-1 DNA binding activity composed of c-Jun, JunB, JunD, 
      and ATF-2 proteins preceded apoptosis. The compositional changes of AP-1 were
      associated with an elevation of c-Jun and JunB protein levels and the appearance 
      of phosphorylated c-Jun and ATF-2 at 15-40 h posttreatment. Immunocytochemistry
      and staining with Hoechst 33258 revealed an accumulation of phosphorylated c-Jun 
      protein in apoptotic cells. Because c-Jun expression and transcriptional activity
      are stimulated by phosphorylation at Ser63/73 by c-Jun N-terminal kinase (JNK),
      we measured JNK activities. We found prolonged induction of JNK activity in
      extracts from cyclosporin-treated cells, which suggests an involvement of
      persistent JNK activation in the initiation of glioma cell apoptosis. We provided
      evidence that variations in AP-1 composition and phosphorylation resulted in
      modification of trans-activating potential toward different promoters. Whereas
      collagenase AP-1/TRE-dependent transcription was down-regulated during apoptosis,
      Fas ligand promoter became activated.
FAU - Pyrzynska, B
AU  - Pyrzynska B
AD  - Department of Cellular Biochemistry, Nencki Institute of Experimental Biology,
      Warsaw, Poland.
FAU - Mosieniak, G
AU  - Mosieniak G
FAU - Kaminska, B
AU  - Kaminska B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Transcription Factor AP-1)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis/physiology
MH  - Cell Division
MH  - Cyclosporine/*pharmacology
MH  - Glioma/metabolism/pathology/*physiopathology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/physiology
MH  - Rats
MH  - Transcription Factor AP-1/chemistry/metabolism/*physiology
MH  - Transcriptional Activation/*physiology
MH  - Tumor Cells, Cultured/drug effects
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1046/j.1471-4159.2000.0740042.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Jan;74(1):42-51. doi: 10.1046/j.1471-4159.2000.0740042.x.