Scientific background: |
CISH(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 CISH 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. CIS 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 CIS. Gain- and loss-of-function studies showed that CIS accelerated degradation of IKBA and
enhanced NFKB activation in cholangiocytes in response to LPS stimulation or C parvum exposure. |
References: |
1. Hu, G., Zhou, R., Liu, J., Gong, A.-Y., Eischeid, A. N., Dittman, J. W., Chen, X.-M. MicroRNA-98 and
let-7 confer cholangiocyte expression of cytokine-inducible Src homology 2-containing protein in
response to microbial challenge. J. Immun. 183: 1617-1624, 2009.
2. Khor, C. C., Vannberg, F. O., Chapman, S. J., Guo, H., Wong, S. H., Walley, A. J., Vukcevic, D.,
Rautanen, A., Mills, T. C., Chang, K.-C., Kam, K.-M., Crampin, A. C., and 23 others. CISH and
susceptibility to infectious diseases. New Eng. J. Med. 362: 2092-2101, 2010.
3. Uchida, K., Yoshimura, A., Inazawa, J., Yanagisawa, K., Osada, H., Masuda, A., Saito, T., Takahashi,
T., Miyajima, A., Takahashi, T. Molecular cloning of CISH, chromosome assignment to 3p21.3, and
analysis of expression in fetal and adult tissues. Cytogenet. Cell Genet. 78: 209-212, 1997 |