PMID- 10359822
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 12
DP  - 1999 Jun 8
TI  - Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of
      the murine SOCS-3 promoter.
PG  - 6964-9
AB  - Pituitary corticotroph SOCS-3 is a novel intracellular regulator of leukemia
      inhibitory factor (LIF)-mediated proopiomelanocortin gene expression and
      adrenocorticotropic hormone (ACTH) secretion, inhibiting LIF-activated Janus
      kinase-signal transducers and activators of transcription (STAT) signaling in a
      negative autoregulatory loop. We now demonstrate in corticotroph AtT-20 cells
      that LIF-stimulated endogenous SOCS-3 mRNA expression is blocked in stable
      transfectants of SOCS-3 wild type or in dominant negative STAT-3 mutants,
      respectively. We characterized approximately 3.8-kb genomic 5' sequence of murine
      SOCS-3, including approximately 2.9-kb sequence upstream of the transcription
      start site (+1), which was determined by 5' rapid amplification of cDNA ends and 
      RNase protection assay. Different 5' constructs were cloned into the pGL3Basic
      vector, and luciferase activity was assayed in transiently transfected
      ACTH-secreting corticotroph AtT-20 cells. A STAT-1/STAT-3 binding element,
      located at nucleotides -72 to -64, was essential for LIF stimulation of SOCS-3
      promoter activity. LIF induced 10-fold increased luciferase activity in a
      wild-type construct spanning -2757 to +929 bases. However, deletion or point
      mutation of the STAT-1/STAT-3 binding element abrogated LIF action (2- to
      3-fold). Electrophoretic mobility-shift assay analysis confirmed specific binding
      of STAT-1 and STAT-3 to this region. These results characterize the genomic 5'
      region of murine SOCS-3 and identify an important STAT-1/STAT-3 binding element
      therein. Thus, LIF-stimulated SOCS-3 gene expression is at least in part mediated
      by STAT-3 and STAT-1. The cytokine inhibitor SOCS-3 acts in a negative loop to
      autoregulate its own gene expression, thus limiting its accumulation in the
      corticotroph cell. These results demonstrate a mechanism for corticotroph
      plasticity with rapid "on" and "off" ACTH induction in response to
      neuro-immuno-endocrine stimuli, such as LIF.
FAU - Auernhammer, C J
AU  - Auernhammer CJ
AD  - Department of Medicine, Cedars-Sinai Research Institute, University of California
      School of Medicine, Los Angeles, CA 90048, USA.
FAU - Bousquet, C
AU  - Bousquet C
FAU - Melmed, S
AU  - Melmed S
LA  - eng
SI  - GENBANK/AF117732
GR  - DK 50238/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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA-Binding Proteins/physiology
MH  - Gene Expression Regulation/*physiology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Pituitary Gland/*physiology
MH  - Promoter Regions, Genetic
MH  - Proteins/*physiology
MH  - RNA, Messenger/analysis
MH  - *Repressor Proteins
MH  - STAT1 Transcription Factor
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/physiology
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins
MH  - Trans-Activators/physiology
MH  - *Transcription Factors
MH  - src Homology Domains
PMC - PMC22025
EDAT- 1999/06/09 00:00
MHDA- 1999/06/09 00:01
CRDT- 1999/06/09 00:00
PHST- 1999/06/09 00:00 [pubmed]
PHST- 1999/06/09 00:01 [medline]
PHST- 1999/06/09 00:00 [entrez]
AID - 10.1073/pnas.96.12.6964 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6964-9. doi: 10.1073/pnas.96.12.6964.