Description
Cytokine inducible SH2-containing protein, also called CIS, CIS-1, G18, SOCS, is an important negative regulator for inflammatory signaling and belongs to the suppressors of cytokine signaling (SOCS) family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. CISH controls interleukin-2 signaling, and variations of CISH with certain SNPs are associated with susceptibility to bacteremia, tuberculosis and malaria. The human gene is mapped to chromosome 3p21.3 by FISH. The mouse gene is tightly linked to the Gnai2 gene on chromosome 9, a region syntenic to human chromosome 3p21. CISH expression was upregulated by lipopolysaccharide (LPS) or Cryptosporidium parvum exposure, and this upregulation involved downregulation of MIR98 and LET7, which relieved MIR98- and LET7-mediated translational repression of CISH. Gain- and loss-of-function studies showed that CISH accelerated degradation of IKBA and enhanced NFKB activation in cholangiocytes in response to LPS stimulation or C parvum exposure