Early responses of trans-activating factors to growth hormone in preadipocytes: Differential regulation of CCAAT enhancer-binding protein-β (C/EBPβ) and C/EBPδ

Clarkson, R. W. E., Chen, C. M., Wells, C., Muscat, G. E. O. and Waters, M. J. (1995) Early responses of trans-activating factors to growth hormone in preadipocytes: Differential regulation of CCAAT enhancer-binding protein-β (C/EBPβ) and C/EBPδ. Molecular Endocrinology, 9 1: 108-120. doi:10.1210/me.9.1.108


Author Clarkson, R. W. E.
Chen, C. M.
Wells, C.
Muscat, G. E. O.
Waters, M. J.
Title Early responses of trans-activating factors to growth hormone in preadipocytes: Differential regulation of CCAAT enhancer-binding protein-β (C/EBPβ) and C/EBPδ
Journal name Molecular Endocrinology   Check publisher's open access policy
ISSN 0888-8809
1944-9917
Publication date 1995-01
Sub-type Article (original research)
DOI 10.1210/me.9.1.108
Volume 9
Issue 1
Start page 108
End page 120
Total pages 13
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract
Using the 3T3-F442A preadipocyte line as a model of GH-dependent differentiation, early changes in the DNA-binding affinity of transcription factors in response to GH addition were investigated. Addition of 50 ng/ml human GH to cells in chemically defined medium led to a rapid increase in binding activity of activator protein 1 (AP-1) and CCAAT enhancer-binding protein (C/EBP), which was significant at 30 min and reached maximal induction by 2 h (3-fold for AP-1, 2.5-fold for C/EBP). Induction in AP-1 DNA binding correlates with a concomitant GH transactivation of c-jun and c-fos genes described previously. Using specific antibodies in electrophoretic mobility shift assays and Western blots, it was shown that the increase in activity of C/EBP is the result of an increase in synthesis of two alternatively translated forms of C/EBPβ: 40-C/EBPβ and 23-C/ EBPβ. This increase in protein was not accompanied by alteration in mRNA level and could be blocked by a Janus kinase 2 tyrosine kinase inhibitor and a C kinase inhibitor at concentrations shown to inhibit GH-dependent activation of microtubule-associated protein (MAP) kinases. Concomitant with the translationally activated increase in C/EBPβ, a GH-dependent increase was observed in C/EBPδ transcription. This was accompanied by an increase in mRNA for C/EBPδ, which was superinduced by cycloheximide and, unlike the increase in C/EBPβ protein, was not observed with insulin. Thus GH exerts its effects on C/EBP isoforms at two levels: transcriptional activation of C/EBPδ and translational activation of C/EBPβ. It is proposed that GH- dependent phosphorylation results in the efficient translation of 40-C/EBPβ and 23-C/ EBPβ (the mouse homolog of the inhibitor liver-enriched inhibitory protein), and that together with the induction of C/EBPδ, these may be involved in initiating the adipocyte differentiation program.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Institute for Molecular Bioscience - Publications
Australian Institute for Bioengineering and Nanotechnology Publications
 
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