Activation of IL-2 receptor alpha-chain gene by individual members of the rel oncogene family in association with serum response factor.
Expression of the IL-2R alpha gene is regulated by members of the c-Rel/NF-kappa B family of transcription factors binding to the kappa B site in the promoter. Previous work has not defined the role of individual members of the c-Rel family in the activation of the IL-2R alpha gene. Using the COS cell system, we were able to reconstitute the regulation of the IL-2R alpha promoter by expressing cloned Rel family members with serum response factor (SRF). We found that c-rel alone activated the IL-2R alpha promoter only weakly but worked with the p50 subunit of NF-kappa B (NFKB1) to give a higher level of expression. We showed that c-rel heterodimerizes with p50 and the amount of this heterodimer correlated with the level of IL-2R alpha gene expression. Our results provide evidence that c-rel/p50 heterodimers activate gene expression in the context of a cellular promoter. We show that c-rel or p65 can cooperate with SRF in the activation of this promoter and the transactivation by c-rel with SRF was enhanced by p50. Synergistic activation required both kappa B and CArG sites, and binding studies show that these adjacent sites can be occupied simultaneously. The transactivation observed with cloned transcription factors mimics the physiologic induction of the IL-2R alpha gene since multiple sequence elements cooperate to give gene activation. The data support the model that c-rel/p50 or p65 can cooperate with SRF to specifically target the expression of the IL-2R alpha gene in activated T cells.
Pierce
J W
JW
Department of Biology, Brandeis University, Waltham, MA 02254, USA.
Jamieson
C A
CA
Ross
J L
JL
Sen
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology; D020569:Proto-Oncogene Proteins c-rel; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D026362:Serum Response Factor; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D015375:Receptors, Interleukin-2; D026362:Serum Response Factor