PMID- 10102627
OWN - NLM
STAT- MEDLINE
DCOM- 19990422
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 8
DP  - 1999 Feb 25
TI  - CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1
      transcriptional activity in mouse keratinocytes.
PG  - 1569-79
AB  - Previously, we have shown that nuclear extracts from cultured mouse keratinocytes
      induced to differentiate by increasing the levels of extra-cellular calcium
      contain Fra-1, Fra-2, Jun B, Jun D and c-Jun proteins that bind to the AP-1 DNA
      binding sequence. Despite this DNA binding activity, AP-1 reporter activity was
      suppressed in these cells. Here, we have detected the CREB family proteins CREB
      and CREMalpha as additional participants in the AP-1 DNA binding complex in
      differentiating keratinocytes. AP-1 and CRE DNA binding activity correlated with 
      the induction of CREB, CREMalpha and ATF-1 and CREB phosphorylation at ser133
      (ser133 phospho-CREB) in the transition from basal to differentiating
      keratinocytes, but the activity of a CRE reporter remained unchanged. In
      contrast, the CRE reporter was activated in the presence of the dominant-negative
      (DN) CREB mutants, KCREB and A-CREB, proteins that dimerize with CREB family
      members and block their ability to bind to DNA. The increase in CRE reporter
      activity in the presence of these mutants suggests that CRE-mediated
      transcriptional activity is suppressed in keratinocytes through protein-protein
      interactions involving a factor that dimerizes with the CREB leucine zipper. In
      experiments where the A-CREB mutant was co-transfected with an AP-1 reporter
      construct, transcriptional activity was also increased indicating that a CREB
      family member binds AP-1 sites and represses AP-1 transcriptional activity as
      well. Exogenous expression of the transcriptional repressor CREMalpha
      down-regulated both CRE and AP-1 reporters in keratinocytes suggesting that this 
      factor may contribute to the suppression of AP-1 transcriptional activity
      observed in differentiating keratinocytes.
FAU - Rutberg, S E
AU  - Rutberg SE
AD  - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic
      Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 
      20892, USA.
FAU - Adams, T L
AU  - Adams TL
FAU - Olive, M
AU  - Olive M
FAU - Alexander, N
AU  - Alexander N
FAU - Vinson, C
AU  - Vinson C
FAU - Yuspa, S H
AU  - Yuspa SH
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
RN  - 9007-49-2 (DNA)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Calcium/physiology
MH  - Cell Differentiation
MH  - Cyclic AMP Response Element Modulator
MH  - Cyclic AMP Response Element-Binding Protein/metabolism/*pharmacology
MH  - DNA/*metabolism
MH  - DNA-Binding Proteins/metabolism/*pharmacology
MH  - Dimerization
MH  - Keratinocytes/*metabolism
MH  - Leucine Zippers
MH  - Macromolecular Substances
MH  - Mice
MH  - Phosphorylation
MH  - Protein Multimerization
MH  - Protein Processing, Post-Translational
MH  - *Repressor Proteins
MH  - Transcription Factor AP-1/*antagonists & inhibitors/metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - 10.1038/sj.onc.1202463 [doi]
PST - ppublish
SO  - Oncogene. 1999 Feb 25;18(8):1569-79. doi: 10.1038/sj.onc.1202463.