Involvement of HNF-1 in the regulation of phosphoenolpyruvate carboxykinase gene expression in the kidney

Hanoch Cassuto, Yael Olswang, Alejandro F. Livoff, Hovav Nechushtan, Richard W. Hanson, Lea Reshef

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK) gene is differentially expressed in several tissues. A specific see of regulatory elements in the promoter are responsible for the control of PEPCK gene transcription and, in turn, determine its distinct metabolic role in each tissue. DNase I footprinting analysis of the PEPCK promoter, using nuclear proteins from tissues which express the gene for PEPCK, and transient expression assays in renal cell lines have demonstrated that the HNF-1 recognition motif (P2) in the PEPCK promoter characterizes kidney-specific expression. This site is required also far the response to acidosis. Since the P2 site is net involved in the expression of the PEPCK gene in the liver, we propose that its critical role in the kidney stems from a combination of abundance of HNF-1 together with low concentrations of members of the C/EBP family in this tissue.

Original languageEnglish
Pages (from-to)597-602
Number of pages6
JournalFEBS Letters
Volume412
Issue number3
DOIs
StatePublished - 4 Aug 1997
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by grant 9100268 from the United States-Israel Binational Foundation (BSF), Jerusalem, Israel, and in part by a grant from the Ministry of Health. We thank Dr. N. Curthoys for the cell line PK1F + . We also acknowledge Drs. P. Monaci, A. Nicosia and S. Cereghini for the expression vector plasmids encoding the liver and kidney-enriched transcription factors HNF-1 and vHNF1. We are grateful to Dr. Meyuhas for the continuous and fruitful discussions along the entire project and for critically reading the manuscript.

Keywords

  • Basal
  • HNF-1
  • Kidney
  • Modulation
  • PEPCK
  • Transcription

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