STAMP, a Novel Predicted Factor Assisting TIF2 Actions in Glucocorticoid Receptor-Mediated Induction and Repression

Abstract

The coactivator TIF2 was predicted to interact with an unknown factor to modify both the relative inhibition in glucocorticoid receptor (GR)-mediated gene repression and several parameters of agonists and antisteroids in GR-regulated induction. Here, we describe the isolation and characterization of the predicted factor as a new 1,277-amino-acid endogenous protein (STAMP). STAMP associates with coactivators (TIF2 and SRC-1) and is selective for a subset of the steroid/nuclear receptors including GRs. Transfected STAMP increases the effects of TIF2 in GR-mediated repression and induction. Conversely, the levels of both induction and repression of endogenous genes are reduced when STAMP small interfering RNAs are used to lower the level of endogenous STAMP. Endogenous STAMP colocalizes with GR in intact cells and is recruited to the promoters of endogenous GR-induced and -repressed genes. We suggest that STAMP is an important new, downstream component of GR action in both gene activation and gene repression.

We thank Kai Ge, Donald McDonnell, Takahiro Nagase, Inez Rogatsky, Liang-Nian Song, and Keith Yamamoto for generously donating reagents; Ami Aronheim (TIIT, Israel) for help on the yeast Sos-recruitment system; Tao Tao (NCBI, NIH) for assistance with the bioinformatic analysis; Dongqing Wang (NIDDK, NIH) for technical assistance; and Inez Rogatsky, Gordon Hager (NCI, NIH), and members of the Steroid Hormones Section for helpful comments about the manuscript.

This research was supported by the Intramural Research Program of the NIH, NIDDK.