The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2 response elements

Immunity. 2001 Jul;15(1):159-72. doi: 10.1016/s1074-7613(01)00167-4.


The interleukin-2 receptor alpha (IL-2Ralpha) chain is an essential component of high-affinity IL-2 receptors. Accordingly, IL-2Ralpha expression helps to regulate T cell growth and other lymphoid functions. Lineage-restricted and activation-dependent IL-2Ralpha transcription is controlled by three upstream positive regulatory regions (PRRs). We now describe an additional IL-2 response element, PRRIV, within intron 1, in humans and mice. PRRIV activity requires GAS motifs that bind Stat5 proteins and additional upstream HMG-I(Y) binding sites. Moreover, IL-2 induces the binding of HMG-I(Y), Stat5a, and Stat5b in vivo to PRRIV and PRRIII, which also functions as an IL-2 response element. Thus, the IL-2 inducibility of the IL-2Ralpha gene is unexpectedly mediated by two widely separated regulatory Stat5-dependent elements, located both upstream and downstream of the transcription initiation sites.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • DNA-Binding Proteins / metabolism
  • Deoxyribonuclease I / pharmacology
  • Gene Expression Regulation / drug effects*
  • HMGA1a Protein
  • High Mobility Group Proteins / metabolism
  • Humans
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Knockout
  • Milk Proteins*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Receptors, Interleukin-2 / genetics*
  • Response Elements*
  • STAT5 Transcription Factor
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins


  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Interleukin-2
  • Milk Proteins
  • Receptors, Interleukin-2
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • STAT5B protein, human
  • Stat5a protein, mouse
  • Stat5b protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • HMGA1a Protein
  • Deoxyribonuclease I

Associated data

  • GENBANK/AF243502
  • GENBANK/AF243503