ISG15 and ISGylation: Emergence in the cytoskeleton dynamic and tumor microenvironment

Cytoskeletal remodeling affects the shape, adhesion, and motility of cells. Cytoskeletal dynamics are modulated by matrix proteins, integrins, and several cytokines in the tumor microenvironment. In this scenario, signaling is activated by integrins and interferons, which can induce ISG15 gene expression. This gene encodes a ubiquitin-like protein that functions as a protein modifier via the ISGylation system. Furthermore, non-conjugated ISG15 acts as a cytokine-like protein. In this viewpoint, the interplay between free ISG15, protein ISGylation, and cytoskeletal dynamics in the tumor microenvironment is discussed.