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Nat Commun. 2013;4:1909. doi: 10.1038/ncomms2916.

Sam68 modulates the promoter specificity of NF-κB and mediates expression of CD25 in activated T cells.

Author information

1
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21025, USA.

Abstract

CD25, the alpha chain of the interleukin-2 receptor, is expressed in activated T cells and has a significant role in autoimmune disease and tumorigenesis; however, the mechanisms regulating transcription of CD25 remain elusive. Here we identify the Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel non-Rel component in the nuclear factor-kappaB (NF-κB) complex that confers CD25 transcription. Our results demonstrate that Sam68 has an essential role in the induction and maintenance of CD25 in T cells. T-cell receptor engagement triggers translocation of the inhibitor of NF-κB kinase alpha (IKKα) from the cytoplasm to the nucleus, where it phosphorylates Sam68, causing complex formation with NF-κB in the nucleus. These findings reveal the important roles of KH domain-containing components and their spatial interactions with IKKs in determining the binding targets of NF-κB complexes, thus shedding novel insights into the regulatory specificity of NF-κB.

PMID:
23715268
PMCID:
PMC3684077
DOI:
10.1038/ncomms2916
[Indexed for MEDLINE]
Free PMC Article

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