Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins

  title={Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins},
  author={Vigo Heissmeyer and Fernando Macian and Sin-Hyeog Im and Rajat Varma and Stefan Feske and K. Venuprasad and Hua Gu and Yun-cai Liu and Michael L. Dustin and Anjana Rao},
  journal={Nature Immunology},
Sustained calcium signaling induces a state of anergy or antigen unresponsiveness in T cells, mediated through calcineurin and the transcription factor NFAT. We show here that Ca2+-induced anergy is a multistep program that is implemented at least partly through proteolytic degradation of specific signaling proteins. Calcineurin increased mRNA and protein of the E3 ubiquitin ligases Itch, Cbl-b and GRAIL and induced expression of Tsg101, the ubiquitin-binding component of the ESCRT-1 endosomal… CONTINUE READING
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