title: The DNA-binding and tau2 transactivation domains of the rat glucocorticoid receptor constitute a nuclear matrix-targeting signal.
abstract: Using an ATP-depletion paradigm to augment glucocorticoid receptor (GR) binding to the nuclear matrix, we have identified a minimal segment of the receptor that constitutes a nuclear matrix targeting signal (NMTS). While previous studies implicated a role for the receptor's DNA-binding domain in nuclear matrix targeting, we show here that this domain of rat GR is necessary, but not sufficient, for matrix targeting. A minimal NMTS can be generated by linking the rat GR DNA-binding domain to either its tau2 transactivation domain in its natural context, or a heterologous transactivation domain derived from the Herpes simplex virus VP16 protein. The transactivation and nuclear matrix-targeting activities of tau2 are separable, as transactivation mutants were identified that either inhibited or had no apparent effect on matrix targeting of tau2. A functional interaction between the NMTS of rat GR and the RNA-binding nuclear matrix protein hnRNP U was revealed in cotransfection experiments in which hnRNP U overexpression was found to interfere with the transactivation activity of GR derivatives that possess nuclear matrix-binding capacity. We have therefore ascribed a novel function to a steroid hormone transactivation domain that could be an important component of the mechanism used by steroid hormone receptors to regulate genes in their native configuration within the nucleus.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: R H
authors.initials: RH
authors.lastname: Getzenberg
authors.forename: B N
authors.initials: BN
authors.lastname: Vietmeier
authors.forename: M R
authors.initials: MR
authors.lastname: Stallcup
authors.forename: M
authors.initials: M
authors.lastname: Eggert
authors.forename: R
authors.initials: R
authors.lastname: Renkawitz
authors.forename: D B
authors.initials: DB
authors.lastname: DeFranco
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D019913:Nuclear Localization Signals; D012313:RNA / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D019913:Nuclear Localization Signals; D011965:Receptors, Glucocorticoid; D012261:Ribonucleoproteins; D012313:RNA; D000255:Adenosine Triphosphate; D004247:DNA