SOCS1: phosphorylation, dimerization and tumor suppression

Abstract

Suppressor of cytokine signaling (SOCS) family members are upregulated following JAK-STAT pathway activation by cytokines. SOCS proteins are recognized inhibitors of cytokine signaling playing roles in cell growth and differentiation. Moreover, SOCS1 and SOCS3 have been shown to be involved in tumor suppression through their ability to interact with p53 leading to the activation of its transcriptional program and showing the implication of SOCS family members in the regulation of apoptosis, ferroptosis and senescence. More recently, we demonstrated that the SRC family of non-receptor tyrosine kinases (SFK) can phosphorylate SOCS1 leading to its homodimerization and inhibiting its interaction with p53. Then, we reactivated the SOCS1-p53 tumor suppressor axis with the SFK inhibitor dasatinib in combination with the p53 activating compound PRIMA. This work suggests new avenues for cancer treatment and leaves open several new questions that deserve to be addressed.