Shank-associated RH domain interactor signaling in tumorigenesis.

Shank-associated RH domain interactor (SHARPIN) is a component of the linear ubiquitin chain activation complex, which is essential for p53 signaling and inflammation. Previous studies have demonstrated that SHARPIN functions in tumor cell survival, growth, invasion and tumorigenesis. These functions include the regulation of p53 proteins via poly-ubiquitination, interaction with a type II protein arginine methyltransferase 5 in melanoma cells, modulating ras-associated protein-1 through p38 and c-Jun N-terminal kinases/c-Jun signaling, and mediating phosphoinositide 3-kinase/AKT signaling via phosphatase and tensin homologue deleted on chromosome 10. Hence, SHARPIN not only participates in the inflammatory response but also serves a critical role in tumor cells. The present review summarizes the biological functions of the absence or presence of SHARPIN with regard to activating the canonical NF-κB signaling pathway and the effects on p53 and other signaling pathways for the modulation of tumorigenesis. Therefore, this review provides insight into the underlying role and mechanisms of SHARPIN in tumorigenesis, as well as its potential application in cancer therapy.