title: Activation of the transcription factor c-Maf in T cells is dependent on the CARMA1-IKKβ signaling cascade.
abstract: The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (T(H)) cell subsets. The amount of c-Maf increases after stimulation of the T cell receptor (TCR), which results in the production of multiple cytokines. We showed that two essential regulators of the transcription factor nuclear factor κB (NF-κB), the scaffold protein CARMA1 and the kinase IKKβ [inhibitor of NF-κB (IκB) kinase β], are also critical for the activation of c-Maf. Although CARMA1 deficiency did not affect the TCR-dependent increase in c-Maf abundance in T cells, CARMA1-dependent activation of the IKK complex was required for the nuclear translocation of c-Maf and its binding to the promoters of its target genes. Consistent with a role for c-Maf in the development of T follicular helper (T(FH)) cells, which provide help to B cells in the germinal centers of the spleen, CARMA1- or IKKβ-deficient mice immunized with peptide antigen had defects in the generation of T(FH) cells, formation of germinal centers, and production of antigen-specific antibodies. Together, these data suggest a mechanism by which c-Maf is regulated during T cell activation and differentiation.
authors.affiliation: 1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Marzenna
authors.initials: M
authors.lastname: Blonska
authors.forename: Donghyun
authors.initials: D
authors.lastname: Joo
authors.forename: Roza I
authors.initials: RI
authors.lastname: Nurieva
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Zhao
authors.forename: Paul
authors.initials: P
authors.lastname: Chiao
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis; D019169:Jurkat Cells; D010047:Ovalbumin / Q000008:administration & dosage; D000090063:Proto-Oncogene Mas; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism*; D015398:Signal Transduction; D000098546:Interleukin-21
chemical_list: D053468:CARD Signaling Adaptor Proteins; D007378:Interleukins; C495607:MAF protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051257:Proto-Oncogene Proteins c-maf; D010047:Ovalbumin; D051550:I-kappa B Kinase; C426242:CARD11 protein, human; D006162:Guanylate Cyclase; D000098546:Interleukin-21