PMID- 12456801
OWN - NLM
STAT- MEDLINE
DCOM- 20030609
LR  - 20211203
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 16
IP  - 12
DP  - 2002 Dec
TI  - Interaction of early growth response protein 1 (Egr-1), specificity protein 1 
      (Sp1), and cyclic adenosine 3'5'-monophosphate response element binding protein 
      (CREB) at a proximal response element is critical for gastrin-dependent 
      activation of the chromogranin A promoter.
PG  - 2802-18
AB  - Recently, binding of specific protein 1 (Sp1) and cAMP response element binding 
      protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical 
      step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric 
      epithelial cells. Here we demonstrate that binding of early growth response 
      protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for 
      gastrin-dependent CgA transactivation. Gastrin elevated cellular and nuclear 
      Egr-1 levels in a time-dependent manner and also increased Egr-1 binding to the 
      CgA -92/-73 region. Disruption of this site reduced gastrin responsiveness 
      without influencing basal promoter activity, while loss of Sp1 and/or CREB 
      binding sites diminished basal and gastrin-stimulated CgA promoter activity. 
      Ectopic Egr-1 overexpression potently stimulated the CgA promoter, whereas 
      coexpression of Egr-1 with Sp1 and/or CREB resulted in additive effects. 
      Functional analysis of Sp1-, Egr-1-, or CREB-specific promoter mutations in 
      transfection studies confirmed the tripartite organization of the CgA -92/-62 
      element. Signaling studies revealed that MAPK kinase 1 (MEK1)/ERK1/2 cascades are 
      critical for gastrin-dependent Egr-1 protein accumulation as well as Egr-1 
      binding to the CgA promoter. Our studies for the first time identify Egr-1 as a 
      nuclear target of gastrin and show that functional interplay of Egr-1, Sp1, and 
      CREB is indispensable for gastrin-dependent CgA transactivation in gastric 
      epithelial cells.
FAU - Raychowdhury, Raktima
AU  - Raychowdhury R
AD  - Medizinische Klink mit Schwerpunkt Gastroenterologie, Hepatologie, Endokrinologie 
      und Stoffwechsel, Universitatsklinikum Charite, Campus Virchow-Klinikum, Humboldt 
      Universitat, 13353 Berlin, Germany.
FAU - Schafer, Georgia
AU  - Schafer G
FAU - Fleming, John
AU  - Fleming J
FAU - Rosewicz, Stefan
AU  - Rosewicz S
FAU - Wiedenmann, Bertram
AU  - Wiedenmann B
FAU - Wang, Timothy C
AU  - Wang TC
FAU - Hocker, Michael
AU  - Hocker M
LA  - eng
GR  - R01 DK 48077/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (CHGA protein, human)
RN  - 0 (Chromogranin A)
RN  - 0 (Chromogranins)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Gastrins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Binding Sites
MH  - Cell Nucleus/metabolism
MH  - Chromogranin A
MH  - Chromogranins/*genetics
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - DNA/chemistry/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Early Growth Response Protein 1
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/metabolism
MH  - Flavonoids/pharmacology
MH  - Gastrins/*pharmacology
MH  - Humans
MH  - *Immediate-Early Proteins
MH  - Immunoblotting
MH  - MAP Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Response Elements
MH  - Signal Transduction
MH  - Stomach Neoplasms
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2002/11/29 04:00
MHDA- 2003/06/10 05:00
CRDT- 2002/11/29 04:00
PHST- 2002/11/29 04:00 [pubmed]
PHST- 2003/06/10 05:00 [medline]
PHST- 2002/11/29 04:00 [entrez]
AID - 10.1210/me.2001-0292 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2002 Dec;16(12):2802-18. doi: 10.1210/me.2001-0292.