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Sci. Signal., 17 December 2013
Vol. 6, Issue 306, p. ra110
[DOI: 10.1126/scisignal.2004273]

RESEARCH ARTICLES

Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKKβ Signaling Cascade

Marzenna Blonska1,2, Donghyun Joo1,3, Roza I. Nurieva2,4, Xueqiang Zhao1,2, Paul Chiao1,2,3, Shao-Cong Sun2,3,4, Chen Dong2,4, and Xin Lin1,2,3,4*

1 Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2 Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3 Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
4 Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract: The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (TH) 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 {kappa}B (NF-{kappa}B), the scaffold protein CARMA1 and the kinase IKKβ [inhibitor of NF-{kappa}B (I{kappa}B) 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 (TFH) 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 TFH 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.

* Corresponding author. E-mail: xllin{at}mdanderson.org

Citation: M. Blonska, D. Joo, R. I. Nurieva, X. Zhao, P. Chiao, S.-C. Sun, C. Dong, X. Lin, Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKKβ Signaling Cascade. Sci. Signal. 6, ra110 (2013).

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