The cytokine-inducible SH2-containing (CISH) protein is a member of the suppressor of cytokine signaling (SOCS) family, which regulates intracellular signaling pathways, particularly the JAK-STAT pathway. Discovered in the late 1990s, CISH is induced by cytokines such as IL-2. IL-3. and erythropoietin, and functions as a negative feedback regulator to attenuate cytokine signaling. It contains a central SH2 domain that binds phosphorylated tyrosine residues on cytokine receptors or JAK kinases, targeting them for proteasomal degradation or blocking downstream signal transduction.
CISH plays critical roles in immune homeostasis, hematopoiesis, and cellular stress responses. Dysregulation of CISH has been linked to various diseases, including cancers (e.g., breast, gastric), autoimmune disorders, and infectious diseases. Notably, genetic polymorphisms in CISH are associated with susceptibility to tuberculosis and malaria, highlighting its importance in pathogen defense.
CISH antibodies are essential tools for studying its expression, localization, and interactions in both physiological and pathological contexts. They are widely used in techniques like Western blotting, immunohistochemistry, and co-immunoprecipitation. Recent research explores CISH as a potential therapeutic target or biomarker, particularly in immunotherapy-resistant cancers where its overexpression may contribute to T-cell exhaustion. However, its dual role as both tumor suppressor and promoter in different contexts requires further investigation.