Investigating the role of an atypical dual-specificity phosphatase DUSP28 in mammalian cells

Abstract

Dual-specificity phosphatases (DUSPs) belong to the protein tyrosine phosphatases (PTP) subfamily and dephosphorylate, both serine/threonine and tyrosine residues of proteins and non-protein substrates. A subgroup of DUSPs called ‘atypical’ are associated with cellular processes such as apoptosis and proliferation. Atypical DUSPs share a high degree of similarity with the MKP (mitogen-activated protein kinase) phosphatase subfamily but lack the N-terminal regulatory domain responsible for substrate specificity. Therefore, the atypical-DUSPs possess a single catalytic PTP domain. Recent approaches show that atypical DUSPs are differentially expressed in various cancers. A member of this family is DUSP28, whose biological function remains unexplored. The level of expression (mRNA and protein) of DUSP28 has been shown to be elevated in hepatocellular carcinoma (HCC), pancreatic and breast cancers. Further, its expression has been shown to increase migration, invasion, and viability through the activation of CREB, AKT, and ERK1/2 signaling pathways in pancreatic and breast cancers. DUSP28 also modulates the cell cycle in HCC by arresting the cells in the S phase with a concomitant decrease in G1 phase cells. In this study, we have endeavoured to characterize the localization, function, substrate recognition, and pathways associated with DUSP28 in HeLa cells.