Study of the correlation between phosphatase regenerating liver 1 (PRL-1) and p53, functional characterization of PRL-1 using drosophila model

Abstract

Part 1 The reversible protein phosphorylation by kanases and phosphatases in signal transduction pathways regulates biological functions involved in cellular processes. One of phosphatases, protein tyrosine phosphatase (PTP) catalyzes the hydrolysis of the phosphate monoesters specifically on tyrosine residues and members of the PTP family regulate a variety of cellular processes including cell growth, differentiation, mitotic cell cycle, and oncogenic transformation. Several protein tyrosine phosphatases (PTPs) have been implicated in various diseases and have emerged as one of therapeutic targets. One of protein tyrosine phosphatases (PTPs), phosphatase of regenerating liver (PRL) family has been known to be associated with tumorigenesis and cancer metastasis. However, intracellular signal and biological function of phosphatase of regenerating liver (PRL) family are not clearly elucidated. Recently, it has been reported that phosphatase of regenerating liver (PRL)-1 and phosphatase of regenerating liver (PRL)-2 are involved in the enhanced cell cycle through a decrease in protein level of p21, one of p53 targets, and phosphatase of regenerating liver (PRL)-3 activate PI3K/Akt signaling during promoting the epithelial-mesenchymal transition (EMT). The effects of phosphatases of regenerating liver (PRLs) on p21 expression and PI3K/Akt activation suggest that phosphatases of regenerating liver (PRLs) may be correlated with the levels of the p53 protein regulating p21 expression and related with AKT signaling-mediated mouse double minute 2 (MDM2) phosphorylation. Therefore, I investigated the potential relationship between phosphatase of regenerating liver (PRL)-1 and p53. Most of the p53 target genes, all except mouse double minute 2 (MDM2), constitutively photomorphogenic 1 (COP1), and p53 induced protein with a RING-H2 domain (PIRH2), take functions in apoptosis, senescence, differentiation, anti-angiogenesis, and cell cycle arrest. The previously mentioned ...