A bifunctional intronic element regulates the expression of the arginine/lysine transporter Cat-1 via mechanisms involving the purine-rich element binding protein A (Purα)

Charlie C. Huang, Calin Bogdan Chiribau, Mithu Majumder, Cheng Ming Chiang, Ronald C. Wek, Robert J. Kelm, Kamel Khalili, Martin D. Snider, Maria Hatzoglou

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Expression of the arginine/lysine transporter Cat-1 is highly induced in proliferating and stressed cells via mechanisms that include transcriptional activation. A bifunctional INE (intronic element) within the first intron of the Cat-1 gene was identified and characterized in this study. The INE had high sequence homology to an amino acid response element and was shown to act as a transcriptional enhancer in unstressed cells by binding the transcription factor, purine-rich element binding protein A (Pura). During endoplasmic reticulum stress, binding of Purα to the INE decreased; the element acted as a positive regulator in early stress by binding of the transcription factor ATF4 and as a negative regulator in prolonged stress by binding the stress-induced C/EBP family member, CHOP.Weconclude that transcriptional control of the Cat-1 gene is tightly controlled by multiple cis-DNA elements, contributing to regulation of cationic amino acid transport for cell growth and proliferation. In addition, we propose that genes may use stress-response elements such as the INE to support basal expression in the absence of stress.

Original languageEnglish (US)
Pages (from-to)32312-32320
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number47
DOIs
StatePublished - Nov 20 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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