STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repression.
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.
He
Yuanzheng
Y
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10, Room 8N307B, Bethesda, MD 20892-1772, USA.
Simons
S Stoney
SS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D008969:Molecular Sequence Data; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015854:Up-Regulation
D002352:Carrier Proteins; D018076:DNA, Complementary; D051958:Nuclear Receptor Coactivator 2; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; C517816:TTLL5 protein, human