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CISH
Cytokine-inducible SH2-containing protein is a protein that in humans is encoded by the ''CISH'' gene.〔(【引用サイトリンク】 url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1154 )〕 ''CISH'' orthologs have been identified in most mammals with sequenced genomes. CISH controls interleukin-2 signaling, and variations of ''CISH'' with certain SNPs are associated with susceptibility to bacteremia, tuberculosis and malaria.〔 (Text )〕
== Function ==
The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL-2, IL-3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor.〔
CISH is induced by T cell receptor (TCR) ligation and negatively regulates it by targeting the critical signaling intermediate PLC-gamma-1 for degradation. The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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