Data from Phosphorylation of SOCS1 Inhibits the SOCS1–p53 Tumor Suppressor Axis

• DOI: 10.1158/0008-5472.c.6510758.v1
• Publication Date: 2023-03-31T04:42:23Z
• Authors: Emmanuelle Saint-...; Lian Mignacca; Geneviève Huot; Mariana Acevedo; Karine Moineau-Va...; Viviane Calabrese; Véronique Bourdeau; Marie-Camille Rowell; Subburaj Ilangumaran; Frédéric Lessard; Gerardo Ferbeyre
• Keywords: Src family kinase

<div>Abstract<p>Expression of the suppressor cytokine signaling-1 (SOCS1) is inactivated in hematopoietic and solid cancers by promoter methylation, miRNA-mediated silencing, mutations. Paradoxically, SOCS1 also overexpressed many human cancers. We report here that ability to interact with p53 regulate cellular senescence depends on a structural motif includes tyrosine (Y)80 SH2 domain SOCS1. Mutations this are found at low frequency some cancers, substitution Y80 phosphomimetic residue inhibits p53–SOCS1 interaction its functional consequences, including stimulation transcriptional activity, growth arrest, senescence. Mass spectrometry confirmed phosphorylation cells, new mAb was generated detect presence tissues IHC. A kinase library screen identified SRC family as Y80-SOCS1 kinases. inhibitors potentiated SOCS1–p53 pathway reinforced SOCS1-induced Samples from lymphomas often overexpress displayed activation, constitutive Y80, cytoplasmic localization. Collectively, these results reveal mechanism inactivates suggest inhibition kinases personalized treatment patients may be successful.</p>Significance:<p>These findings show tumor-suppressive indicating increased benefit inhibitors.</p></div>