Growth hormone corrects proliferation and transcription of phosphoenolpyruvate carboxykinase in livers of old mice via elimination of CCAAT/enhancer-binding protein α-Brm complex

Guo Li Wang, Xiurong Shi, Elizabeth Salisbury, Yuxiang Sun, Jeffrey H. Albrecht, Roy G. Smith, Nikolai A. Timchenko

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Growth hormone (GH), which is reduced with age, corrects the impaired proliferative capacity of livers of old animals. In this paper, we present a mechanism by which GH eliminates age-dependent negative control of proliferation and increases transcription of liver-specific genes in livers of old mice. The reduced proliferative capacities of the liver of old animals are associated with the CCAAT/enhancer-binding protein α (C/EBPα)-Brm complex, which inhibits E2F-dependent promoters. We found that a sequestration of C/EBPα into complexes with Brm leads to a weak interaction of C/EBPα with promoters of liver-specific genes, expression of which is reduced in old animals. Injection of either GH or the regulator of the amplitude of endogenous GH release, ghrelin, reduces the C/EBPα-Brm complex in livers of old mice, leading to a derepression of E2F targets, to increased interactions of C/EBPα with promoters of liver-specific genes, and to correction of their expression. GH-dependent elimination of the complex is mediated by the inhibition of cyclin D3-CDK4 activity and by elevation of a phosphatase, protein phosphatase 2A, which dephosphorylates C/EBPα and dissociates the complex.

Original languageEnglish (US)
Pages (from-to)1468-1478
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number2
DOIs
StatePublished - Jan 12 2007
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this