title: Dephosphorylation of TORC initiates expression of the StAR gene.
abstract: Cyclic AMP responsive element (CRE) binding protein (CREB) is known to activate transcription when its Ser133 is phosphorylated. However, transducer of regulated CREB activity (TORC), a CREB specific co-activator, upregulates CREB activity in a phospho-Ser133-independent manner. Interestingly, TORC is also regulated by phosphorylation; the phospho-form is inactive, and the dephospho-form active. When PKA phosphorylates CREB, it inhibits TORC kinases simultaneously and accelerates dephosphorylation of TORC. We show in this report that staurosporine, a kinase inhibitor, induces the expression of the StAR gene in Y1 adrenocortical cells, possibly a result of an increase in the population of dephospho-TORC. The expression of the StAR gene is known to be regulated by SF-1 and CREB, and the co-activators CBP/p300 may mediate the actions of both factors. Our experiments using KG501, a disruptor of the interaction between phospho-CREB and CBP/p300, also support the importance of TORC in the regulation of StAR gene expression.
authors.affiliation: Laboratory of Cell Signaling and Metabolism, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan. takemori@nibio.go.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemori
authors.forename: Mariko
authors.initials: M
authors.lastname: Kanematsu
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Hatano
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Katoh
authors.forename: Xing-Zi
authors.initials: XZ
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Junko
authors.initials: J
authors.lastname: Doi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009284:Naphthols / Q000494:pharmacology; D010755:Organophosphates / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D054339:Steroidogenic Factor 1; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C500984:CRTC1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018398:Homeodomain Proteins; D009284:Naphthols; D010755:Organophosphates; D010750:Phosphoproteins; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; C495860:naphthol AS-E phosphate; D000098682:Steroidogenic Acute Regulatory Protein; D019311:Staurosporine