A novel mechanism for ERK-dependent regulation of IL4 transcription during human Th2-cell differentiation

作者:Tripathi Parul; Sahoo Naresh; Ullah Ubaid; Kallionpaa Henna; Suneja Amita; Lahesmaa Riitta; Rao Kanury V S*
来源:Immunology and Cell Biology, 2012, 90(7): 676-687.
DOI:10.1038/icb.2011.87

摘要

We demonstrate that the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 have a central role in mediating T-cell receptor-dependent induction of IL4 expression in human CD4(+) T cells. Significantly, this involved a novel mechanism wherein receptor cross-linking induced activated ERK to physically associate with a promoter element on the IL4 gene. The proximally localized ERK then facilitated recruitment of the key transcription factors necessary for initiating IL4 gene transcription. Although both ERK-1 and ERK-2 bound to the promoter, recruitment of either one alone was found to be sufficient. We thus identify a novel mode of function for ERK wherein its physical association with the promoter serves as a prerequisite for enhanceosome assembly. This unusual pathway is also indispensable for human Th2-cell differentiation. Immunology and Cell Biology (2012) 90, 676-687; doi:10.1038/icb.2011.87; published online 11 October 2011

  • 出版日期2012-8