Suppressor of cytokine signaling 1

Definition:

Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec protein-tyrosine activity. Regulates IFN-gamma (IFNG)-mediated sensory neuron survival (By similarity). Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

References:

[1]. Jérôme Hadjadj, et al. Early-onset autoimmunity associated with SOCS1 haploinsufficiency. Nat Commun. 2020 Oct 21;11(1):5341. [Content Brief]

[2]. K i Ohya, et al. SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. J Biol Chem. 1997 Oct 24;272(43):27178-82. [Content Brief]

[3]. James E D Thaventhiran, et al. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature. 2020 Jul;583(7814):90-95. [Content Brief]

[4]. S Kamizono, et al. The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2. J Biol Chem. 2001 Apr 20;276(16):12530-8. [Content Brief]

[5]. J Frantsve, et al. Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome-mediated degradation. Mol Cell Biol. 2001 May;21(10):3547-57. [Content Brief]

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