Up-regulation of upstream stimulatory factors by protein malnutrition and its possible role in regulation of the IGF-binding protein-1 gene

Endocrinology
T MatsukawaT Noguchi

Abstract

Protein malnutrition drastically induces the expression of the IGF-binding protein-1 (IGFBP-1) gene. We have previously shown that the region between -77 and -112 bp upstream of the rat IGFBP-1 gene contributes to the response of this gene to amino acid limitation. In an attempt to elucidate the basis of the responsiveness of this putative amino acid response unit (AARU), we searched the nucleus of the rat liver for a trans-acting factor whose binding to AARU was dependent on protein nutrition. Liver nuclear extracts of rats fed a protein-free diet and of those fed a control diet were compared by EMSA using the AARU as probe. One of the protein-probe complexes underwent a drastic increase after dietary protein deprivation. Assays using specific antibodies and several competitor oligonucleotides led to identification of the protein composing the complex as upstream stimulatory factor-1 (USF) and USF-2. The binding site of the USF proteins in the AARU turned out to be a CACGGG sequence that was homologous to the consensus USF-binding sequence (E box; CANNTG). Further, Western blot analyses showed that a protein-free diet caused significant increases in USF-1 and USF-2 levels. Thus, elevated expression of the IGFBP-1 gene under pr...Continue Reading

Citations

Feb 21, 2006·The Journal of Biological Chemistry·Li ChenXing Li Wang
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May 16, 2012·Advances in Nutrition·Michael S KilbergJixiu Shan
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