PMID- 8388998
OWN - NLM
STAT- MEDLINE
DCOM- 19930629
LR  - 20131121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 7
IP  - 4
DP  - 1993 Apr
TI  - Cell-specific bifunctional role of Jun oncogene family members on glucocorticoid 
      receptor-dependent transcription.
PG  - 570-84
AB  - Interaction between protein kinase C (PKC)- and glucocorticoid receptor 
      (GR)-mediated signaling is suggested by the ability of the PKC activating phorbol 
      ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to inhibit GR-dependent 
      transcription of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). 
      Here we report that this interference is cell specific, as TPA augmented 
      dexamethasone-induced transcriptional activation of the MMTV LTR in several T 
      cell lines but was inhibitory in NIH-3T3 fibroblasts. TPA-GR synergism was 
      determined to have occurred at the GR-responsive element (GRE) level by 
      functional analysis of deletion mutants or synthetic GRE oligonucleotides driving 
      chloramphenicol acetyl-transferase expression. Synergism required an intact GR 
      DNA-binding domain, whereas amino- or carboxyl-terminal domains were dispensable. 
      The effect was abrogated by the PKC inhibitor staurosporine, suggesting a role 
      for PKC. Increased c-jun, jun-B, and jun-D expression above basal levels and 
      increased transcriptional activity of AP-1/TPA responsive elements fused to 
      chloramphenicol acetyl-transferase vectors were observed in T cells treated with 
      TPA alone or in combination with dexamethasone. The ability of Jun proteins to 
      cooperate with GR in T cells has been investigated after transfection of c-jun, 
      jun-B, or jun-D expression vectors, which augmented GR-dependent transcription 
      from either MMTV LTR or GRE. Conversely, c-jun and jun-B transfection blunted 
      GR-dependent transcription in HeLa cells. The presence of c-fos had a negative 
      influence on GR function and correlated with the cell-specific synergistic or 
      antagonistic activity of Jun with respect to GR; high basal expression of c-fos 
      as well as AP-1 DNA binding and transcriptional activity were observed in HeLa 
      cells, but not in T cells. Furthermore overexpression of exogenous c-fos has an 
      inhibitory effect on GR-dependent transcription from GRE in T cells. We propose 
      that Jun plays a bifunctional role on GR-dependent transcriptional activation of 
      GRE, selecting either synergistic or antagonistic activity depending on the 
      cell-specific microenvironment. In this regard, intracellular levels of c-fos 
      appear to be influential.
FAU - Maroder, M
AU  - Maroder M
AD  - Department of Experimental Medicine, University La Sapienza, Rome, Italy.
FAU - Farina, A R
AU  - Farina AR
FAU - Vacca, A
AU  - Vacca A
FAU - Felli, M P
AU  - Felli MP
FAU - Meco, D
AU  - Meco D
FAU - Screpanti, I
AU  - Screpanti I
FAU - Frati, L
AU  - Frati L
FAU - Gulino, A
AU  - Gulino A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (DNA, Viral)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
GS  - c-jun
GS  - jun-B
GS  - jun-D
MH  - 3T3 Cells
MH  - Animals
MH  - DNA/metabolism
MH  - DNA, Viral/metabolism
MH  - Dexamethasone/pharmacology
MH  - Genes, jun/*physiology
MH  - HeLa Cells
MH  - Humans
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Protein Kinase C/metabolism
MH  - Receptors, Glucocorticoid/*physiology
MH  - Repetitive Sequences, Nucleic Acid
MH  - Signal Transduction
MH  - T-Lymphocytes/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - *Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
EDAT- 1993/04/01 00:00
MHDA- 1993/04/01 00:01
CRDT- 1993/04/01 00:00
PHST- 1993/04/01 00:00 [pubmed]
PHST- 1993/04/01 00:01 [medline]
PHST- 1993/04/01 00:00 [entrez]
AID - 10.1210/mend.7.4.8388998 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1993 Apr;7(4):570-84. doi: 10.1210/mend.7.4.8388998.