Inhibition of retinoic acid receptor function and retinoic acid-regulated gene expression in mouse melanoma cells by calreticulin. A potential pathway for cyclic AMP regulation of retinoid action

Calcium is a second messenger that controls a wide variety of cellular functions. Because of its multiple actions, there is a stringent requirement for calcium homeostasis, and this is achieved in part by a system of transport and storage proteins such as calreticulin located in the endoplasmic reti...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-06, Vol.271 (25), p.15153-15159
Main Authors: Desai, D, Michalak, M, Singh, N K, Niles, R M
Format: Article
Language:English
Subjects:
8-Bromo Cyclic Adenosine Monophosphate - pharmacology
adenosine monophosphate
adenosinmonofosfato
Animals
calcio
calcium
calcium binding proteins
Calcium-Binding Proteins - biosynthesis
Calcium-Binding Proteins - physiology
Calreticulin
cation
cationes
cations
cell culture
Cell Line
chemoreceptors
chimiorecepteur
cultivo de celulas
culture de cellule
Cyclic AMP - metabolism
Enzyme Induction
gene
Gene Expression Regulation, Neoplastic - drug effects
genes
Isoenzymes - biosynthesis
Kinetics
Melanoma, Experimental - metabolism
Mice
Molecular Chaperones - physiology
Protein Kinase C - biosynthesis
Protein Kinase C-alpha
proteinas que ligan calcio
proteine de liaison calcium
quimioreceptores
raton
Receptors, Retinoic Acid - antagonists & inhibitors
Receptors, Retinoic Acid - biosynthesis
Receptors, Retinoic Acid - metabolism
Recombinant Proteins - biosynthesis
retinol
Ribonucleoproteins - biosynthesis
Ribonucleoproteins - physiology
souris
Transfection
Tretinoin - pharmacology
Tumor Cells, Cultured
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Summary:Calcium is a second messenger that controls a wide variety of cellular functions. Because of its multiple actions, there is a stringent requirement for calcium homeostasis, and this is achieved in part by a system of transport and storage proteins such as calreticulin located in the endoplasmic reticulum. Calreticulin is also found in the nucleus, suggesting that it may have a role in transcriptional regulation. It has been reported that calreticulin can inhibit steroid-regulated gene transcription by preventing receptor binding to DNA. Here we report that overexpression of the calreticulin gene in B16 mouse melanoma cells resulted in a decrease in retinoic acid (RA)-stimulated reporter gene expression. Gel shift analysis showed that purified calreticulin inhibited the binding of endogenous RAR to a beta-RA response element oligonucleotide, only if added prior to the addition of the oligonucleotide. Co-immunoprecipitation studies suggest a physical interaction between RAR and calreticulin. Transfection of the calreticulin gene into B16 cells inhibited the RA induction of protein kinase Calpha, a marker of RA-induced differentiation. We also found that cyclic AMP increased the expression of calreticulin. Cyclic AMP may act to antagonize RA action by both decreasing RAR expression (Y. Xiao, D. Desai, T. Quick, and R.M. Niles, J. Cell Physiol., in press) and stimulating calreticulin levels.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.271.25.15153