Dephosphorylation of TORC initiates expression of the StAR gene.
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.
Takemori
Hiroshi
H
Laboratory of Cell Signaling and Metabolism, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan. takemori@nibio.go.jp
Kanematsu
Mariko
M
Kajimura
Junko
J
Hatano
Osamu
O
Katoh
Yoshiko
Y
Lin
Xing-Zi
XZ
Min
Li
L
Yamazaki
Takeshi
T
Doi
Junko
J
Okamoto
Mitsuhiro
M
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
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