Suppression of T cell function: a potential role for transcriptional repressor ICER.
In this article, we review the inducible cAMP early repressor (ICER) and its possible critical involvement in modulation of T cell responsiveness by its capacity to transcriptionally attenuate interleukin-2 (IL-2) gene expression. It seems clear that the failure to produce the IL-2 is an important determinant of anergy induction. It is important that the CD28-responsive element (CD28RE), a composite DNA binding element consisting of NFAT and cyclic AMP-responsive (CRE)-like motifs in position of -160 of IL-2 promoter has the high affinity for ICER binding as well as NFAT/ICER complex formation. Moreover, CD28RE with adjacent DNA sequences was also shown to be essential for conferring anergy in T lymphocytes. Because ICER does not possess a transactivation domain required for the recruitment of CBP/p300, the binding of ICER to CD28RE and/or composite motifs containing CRE-like DNA motifs may lead to uncoupling of CBP/p300 thus extinguishing IL-2 expression as well as expression of numerous other cytokines and chemokines.
Bodor
J
J
Experimental Immunology Branch, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA.
Bodorova
J
J
Gress
R E
RE
D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008024:Ligands; D011956:Receptors, Cell Surface / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008024:Ligands; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D019204:GTP-Binding Proteins