Androgens regulate the binding of endogenous HuR to the AU-rich 3'UTRs of HIF-1alpha and EGF mRNA

Biochem Biophys Res Commun. 2004 Sep 17;322(2):644-51. doi: 10.1016/j.bbrc.2004.07.173.

Abstract

The 3'UTRs of mammalian HIF-1alpha and EGF mRNA contain several highly conserved AU-rich elements (ARE) known to control the turnover of labile mRNAs by binding ARE-binding proteins that regulate nucleocytoplasmic shuttling, translation, and degradation. Androgens regulate the level and subcellular shuttling of HuR, a major ARE-binding protein that stabilizes many ARE-mRNAs. Pull down of biotinylated 3'UTRs of HIF-1alpha or EGF enriches HuR on blots from Jurkat cell lysates 5-fold, and enriches the amount of RNase-protected biotinylated RNA that comigrates with HuR approximately 10-fold. Dihydrotestosterone treatment decreases the HuR-protected riboprobe pulled down from total Jurkat cell lysates by 30-40%, apparently reflecting shifts in HuR from the nucleus to the cytoplasm. Androgen treatment also changes the amount of HuR-protected riboprobe pulled down from a PC-3 clone expressing a functional androgen receptor. The shift in the amount of riboprobe bound by HuR suggests that androgen is up-regulating endogenous ARE-mRNAs that can compete for binding endogenous HuR. These changes in the shuttling and ARE-binding of endogenous HuR indicate that androgen can act posttranscriptionally to regulate ARE-mRNAs, including HIF-1alpha and EGF.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Androgens / metabolism
  • Antigens, Surface / metabolism*
  • DNA-Binding Proteins / metabolism
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Epidermal Growth Factor / genetics*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immediate-Early Proteins / metabolism
  • Jurkat Cells
  • Molecular Probes
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Transcription Factors / genetics*
  • Tristetraprolin

Substances

  • 3' Untranslated Regions
  • Androgens
  • Antigens, Surface
  • DNA-Binding Proteins
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immediate-Early Proteins
  • Molecular Probes
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors
  • Tristetraprolin
  • ZFP36 protein, human
  • Epidermal Growth Factor