The Role Of C-Src Sumoylation In Tumorigenesis

c-Src,encoded by proto-oncogene SRC,belongs to a family of non-receptor tyrosine kinase proteins.c-Src contains several conserved domains such as N-terminal myristylation sequence,SH4 domain for membrane localization,SH3 domain binding to proline-rich peptide,SH2 domain recognizing specific tyrosine phosphopeptide motif,SH1 domain for tyrosine kinase activity and C-terminal negative regulatory region.High expression level or kinase activity of c-Src have been found in a number of human tumors,and the aberrant activation of c-Src regulates multiple aspects during tumor progression,such as apoptosis,proliferation,cell adhesion,cell migration and invasion,angiogenesis and metastasis.SUMOyaltion is a vital post-translational modification,which affects target protein activity,subcellular localization,stability and protein-protein interaction,and further regulates cell cycle,growth,differentiation and migration.In this study we wondered if c-Src could be SUMOylated and what is its role in tumorigenesis.We identified that c-Src can be SUMOylated by SUMO1 at Lysine 318(K318)in 293 T overexpression system and prokaryotic expression system.Furthermore,we constructed c-Src knockdown stable cell lines,after that we re-expression wild type c-Src and SUMO deficient c-Src K318 R in stable cell lines.As shown in results,the SUMO-deficient c-Src K318 R stable cell line is more malignant in tumorigenesis.Correspondingly,c-Src SUMOylation could decrease the phosphorylation level of FAK at Tyr925 site but has no effect on FAK binding and other proteins,such as EGFR,RPTP? and CSK.In summary,our evidences show that c-Src is SUMOylated in vivo and this modification can reduce phosphorylation of FAK Tyr925.Thus,SUMOylation of c-Src delays tumorgenesis,which is a new clue for clinical treatment.