RAP46 Is a Negative Regulator of Glucocorticoid Receptor Action and Hormone-induced Apoptosis

RAP46 was first identified by its ability to bind the glucocorticoid receptor. It has since been reported to bind several cellular proteins, including the anti-apoptotic protein Bcl-2, but the biological significance of these interactions is unknown. Here we show that RAP46 binds the hinge region of...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1998-06, Vol.273 (23), p.14620-14625
Main Authors: Kullmann, Michael, Schneikert, Jean, Moll, Jürgen, Heck, Stefanie, Zeiner, Matthias, Gehring, Ulrich, Cato, Andrew C.B.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Carrier Proteins - metabolism
Carrier Proteins - physiology
Dexamethasone - pharmacology
DNA-Binding Proteins - metabolism
Down-Regulation - physiology
Flow Cytometry
Gene Expression Regulation - genetics
Glucocorticoids - pharmacology
Humans
Mice
Polyenes - pharmacology
Protein Binding - physiology
Receptors, Glucocorticoid - metabolism
Sirolimus
Transcription Factors
Transcriptional Activation - physiology
Transfection
Tumor Cells, Cultured
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:RAP46 was first identified by its ability to bind the glucocorticoid receptor. It has since been reported to bind several cellular proteins, including the anti-apoptotic protein Bcl-2, but the biological significance of these interactions is unknown. Here we show that RAP46 binds the hinge region of the glucocorticoid receptor and inhibits DNA binding and transactivation by the receptor. We further show that overexpression of RAP46 in mouse thymoma S49.1 cells inhibits glucocorticoid-induced apoptosis. Conversely, glucocorticoid-induced apoptosis and transactivation were enhanced after treating S49.1 cells with the immunosuppressant rapamycin, which down-regulates cellular levels of BAG-1, the mouse homolog of RAP46. The effect of rapamycin can, however, be overcome by overexpression of RAP46. These results together identify RAP46 as a protein that controls glucocorticoid-induced apoptosis through its negative regulatory action on the transactivation property of the glucocorticoid receptor.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.23.14620