PMID- 11127825
OWN - NLM
STAT- MEDLINE
DCOM- 20001228
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 19
IP  - 51
DP  - 2000 Nov 30
TI  - Involvement of c-Fos in signaling grp78 induction following ER calcium release.
PG  - 5936-43
AB  - Release of calcium from the endoplasmic reticulum (ER) signals an increase in 
      transcription of both the early response gene, c-fos, and the late response gene, 
      grp78. We have used thapsigargin (TG), an ER calcium-ATPase pump inhibitor that 
      induces calcium release from the ER, to investigate the possible involvement of 
      c-Fos, a component of the AP-1 transcription factor, in grp78 induction. Two cell 
      lines with markedly different responses to TG treatment were employed: the 
      WEHI7.2 mouse lymphoma line in which TG fails to induce grp78, and the MDA-MB-468 
      mammary epithelial line in which TG induces grp78. In WEHI7.2 cells, TG-induced 
      calcium release triggers a rapid increase in c-fos mRNA, but the level of c-Fos 
      protein decreases due to degradation by the multicatalytic proteasome. 
      C-FosdeltaC, a proteasome resistant c-Fos mutant with AP-1 activity similar to 
      that of wild type c-Fos, restores grp78 induction in WEHI7.2 cells, detected by 
      both Northern hybridization and a grp78 promoter-luciferase reporter assay. In 
      MDA-MB-468 cells, TG-mediated calcium release induces a sustained elevation of 
      c-Fos protein that precedes grp78 induction. A region of the grp78 promoter 
      containing both ERSE and CORE regions, but missing TRE and CRE regions, is 
      sufficient to mediate induction of reporter luciferase activity. Induction of 
      this reporter was blocked by A-Fos, a dominant negative inhibitor of c-Fos. Also, 
      the induction of grp78-luciferase reporter activity was inhibited by c-fos 
      antisense mRNA. In summary, the findings indicate that c-Fos is involved in 
      signaling grp78 induction following TG treatment, and that grp78 induction is 
      inhibited by proteasome-mediated c-Fos degradation.
FAU - He, H
AU  - He H
AD  - Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, 
      USA.
FAU - McColl, K
AU  - McColl K
FAU - Distelhorst, C W
AU  - Distelhorst CW
LA  - eng
GR  - CA79806/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carrier Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Breast/drug effects/physiology
MH  - Calcium/*physiology
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Carrier Proteins/biosynthesis/*genetics
MH  - Endoplasmic Reticulum/*metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/drug effects/physiology
MH  - Gene Expression Regulation/physiology
MH  - *Heat-Shock Proteins
MH  - Humans
MH  - Molecular Chaperones/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins c-fos/antagonists & inhibitors/genetics/*physiology
MH  - RNA, Antisense/genetics/pharmacology
MH  - RNA, Messenger/genetics
MH  - Signal Transduction/*physiology
MH  - Thapsigargin/pharmacology
MH  - Transcription Factor AP-1/biosynthesis/physiology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2000/12/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/29 11:00
PHST- 2000/12/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/29 11:00 [entrez]
AID - 10.1038/sj.onc.1203994 [doi]
PST - ppublish
SO  - Oncogene. 2000 Nov 30;19(51):5936-43. doi: 10.1038/sj.onc.1203994.