Abstract
Src, a non-receptor tyrosine kinase protein, plays a critical role in cell proliferation and tumorigenesis. SUMOylation, a reversible ubiquitination-like post-translational modification, is vital for tumor progression. Here, we report that the Src protein can be SUMOylated at lysine 318 both in vitro and in vivo. Hypoxia can induce a decrease of Src SUMOylation along with an increase of Y419 phosphorylation, a phosphorylation event required for Src activation. On the other hand, treatment with hydrogen peroxide can enhance Src SUMOylation. Significantly, ectopic expression of SUMO-defective mutation, Src K318R, promotes tumor growth more potently than that of wild-type Src, as determined by migration assay, soft agar assay, and tumor xenograft experiments. Consistently, Src SUMOylation leads to a decrease of Y925 phosphorylation of focal adhesion kinase (FAK), an established regulatory event of cell migration. Our results suggest that SUMOylation of Src at lysine 318 negatively modulate its oncogenic function by, at least partially, inhibiting Src-FAK complex activity.