ATP-stimulated translocation promoter that enhances the nuclear binding of activated glucocorticoid receptor complex. Biochemical properties and its function (mini-review).
Association of nonhormone binding proteins with steroid receptor protein as well as modifications of the receptor by ATP, PPi, pyridoxal 5'-phosphate, molybdate, and the large number of less-well-characterized factors are important for the modulation and control of signal transduction in the steroid-receptor systems. Each of the steps in the steroid-receptor system, that is, the steroid binding, nuclear binding, DNA binding, and transcriptional regulations of specific genes (glucocorticoid response elements; GREs), may be controlled by the receptor interactions with other proteins and modulators. During the study on the regulatory mechanism of glucocorticoid-receptor system, we found a new endogenous factor in rat liver cytosol that increases the binding of activated glucocorticoid-receptor complex (GRC) to nuclei in the presence of ATP, and we named this factor ATP-stimulated translocation promoter (ASTP). Recently, we have purified ASTP protein to homogeneity and characterized it. ASTP has an M(r) of 93,000, and is composed of two apparently identical subunits with M(r) of 48,000. The sedimentation coefficient of ASTP is 6.5S, and its isoelectric point is 4.5. ASTP increases the binding of activated GRC to nuclei and chromatin, but not to DNA. ASTP activity is dependent on the physiological concentration of ATP, although ASTP does not bind to ATP-agarose. Interestingly, ASTP can bind to the arginine-rich histones H3 and H4, to which activated GRC also binds. In this article, we will summarize the biochemical properties of this interesting protein (ASTP) and will discuss our thinking about the mode of action.
Isohashi
F
F
Department of Oncology, Osaka University Medical School, Japan.
Okamoto
K
K
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D000255:Adenosine Triphosphate