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

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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

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CCAAT-Enhancer-Binding Proteins
Phosphoenolpyruvate
Transcription
Liver
Growth Hormone
Animals
Genes
Cyclin D3
Protein Phosphatase 2
Ghrelin
Phosphatases
Phosphoric Monoester Hydrolases
Gene expression
Gene Expression
Injections

ASJC Scopus subject areas

  • Biochemistry

Cite this

Growth hormone corrects proliferation and transcription of phosphoenolpyruvate carboxykinase in livers of old mice via elimination of CCAAT/enhancer-binding protein α-Brm complex. / Wang, Guo Li; Shi, Xiurong; Salisbury, Elizabeth; Sun, Yuxiang; Albrecht, Jeffrey H.; Smith, Roy G.; Timchenko, Nikolai A.

In: Journal of Biological Chemistry, Vol. 282, No. 2, 12.01.2007, p. 1468-1478.

Research output: Contribution to journalArticle

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