Dephosphorylation of TORC initiates expression of the StAR gene

Mol Cell Endocrinol. 2007 Feb:265-266:196-204. doi: 10.1016/j.mce.2006.12.020. Epub 2007 Jan 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Viral
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Gene Expression Regulation / drug effects
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Naphthols / pharmacology
  • Organophosphates / pharmacology
  • Phosphoproteins / genetics*
  • Phosphorylation
  • Protein Isoforms / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Staurosporine / pharmacology
  • Steroidogenic Factor 1
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*

Substances

  • CRTC1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Homeodomain Proteins
  • Naphthols
  • Organophosphates
  • Phosphoproteins
  • Protein Isoforms
  • Protein Kinase Inhibitors
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Trans-Activators
  • Transcription Factors
  • naphthol AS-E phosphate
  • steroidogenic acute regulatory protein
  • Staurosporine