Prolyl Endopeptidase Is Involved in Cellular Signalling in Human Neuroblastoma SH-SY5Y Cells

Abstract

Prolyl endopeptidase (PREP), probably acting through the inositol cycle, has been implicated in memory and learning. However, the physiological role of PREP is unknown. It has been shown that PREP expression, regulated in cerebellar granule cells, has probably a role in cell proliferation and differentiation. Here, we report the levels and subcellular distribution of PREP in human neuroblastoma SH-SY5Y cells in proliferating conditions and under differentiation induced by retinoic acid (RA). We analysed the levels of cell signalling intermediates, growth behavior and gene expression, and differentiation morphology changes, upon PREP inhibition. After induction of differentiation, PREP activity was found decreased in the nucleus but increased to high levels in the cytoplasm, due in part to increased PREP transcription. The levels of inositol (1,4,5)-trisphosphate revealed no correlation with PREP activity, but phosphorylated extracellular signal-regulated kinases 1 and 2 were decreased by PREP inhibition during early stages of differentiation. Morphological evaluation indicated that PREP inhibition retarded the onset of differentiation. PREP activity regulated gene expression of protein synthesis machinery, intracellular transport and kinase complexes. We conclude that PREP is a regulatory target and a regulatory element in cell signalling. This is the first report of a direct influence of a cell signalling molecule, RA, on PREP expression.

Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells

“…ERK signaling plays an important role in progesterone secretion in luteal cells (Dewi, Abayasekara, & Wheeler‐Jones, ; Tai, Chang, Leung, & Tzeng, ). Studies have shown that POP can regulate the ERK signaling pathway (Moreno‐Baylach et al, ). Therefore, we examine the ERK1/2 phosphorylation in luteal cells using western blot analysis.…”

Prolyl Endopeptidase Activity Is Correlated with Colorectal Cancer Prognosis

“…Assays in cell cultures and in animal models show that some of its natural substrates, like angiotensins and thymosin β4, are implicated in cell growth, angiogenesis and apoptosis 23, 37, 38. Some authors suggest that potentially coordinated actions of this enzyme with matrix metalloproteinases are at the base of some inflammatory conditions 39, and still others advocate that PEP regulates the angiogenesis and cell growth independently from its catalytic action 17,40,41. As stated in other peptidases 6, 42, these data suggest that PEP is a multifunctional protein.…”

OsPOP5, A Prolyl Oligopeptidase Family Gene from Rice Confers Abiotic Stress Tolerance in Escherichia coli

“…Recently, POP was reported to have roles associated with cell cycle regulation [42], angiogenesis [43] and cellular signaling [44]. In addition, there appears to be some consensus that POP possesses a non-hydrolase function and it was demonstrated that POP is located in close association with the cytoskeletal component tubulin [41].…”