title: Prolidase-proline dehydrogenase/proline oxidase-collagen biosynthesis axis as a potential interface of apoptosis/autophagy.
abstract: Prolidase is a cytosolic imidodipeptidase that specifically splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline from imidodipeptides for resynthesis of collagen and other proline-containing proteins. The mechanism of prolidase-dependent regulation of collagen biosynthesis was found at both transcriptional and post-transcriptional level. The increase in the enzyme activity is due to its phosphorylation on serine/threonine residues. Prolidase-dependent transcriptional regulation of collagen biosynthesis was found at the level of NF-κB, known inhibitor of type I collagen gene expression. Proline dehydrogenase/proline oxidase (PRODH/POX) is flavin-dependent enzyme associated with the inner mitochondrial membrane. The enzyme catalyzes conversion of proline into Δ(1) -pyrroline-5-carboxylate (P5C), during which reactive oxygen species (ROS) are produced, inducing intrinsic and extrinsic apoptotic pathways. Alternatively, under low glucose stress, PRODH/POX activation produces ATP for energy supply and survival. Of special interest is that PRODH/POX gene is induced by P53 and peroxisome proliferator-activated gamma receptor (PPARγ). Among down-regulators of PRODH/POX is an oncogenic transcription factor c-MYC and miR-23b*. On the other hand, PRODH/POX suppresses HIF-1α transcriptional activity, the MAPK pathway, cyclooxygenase-2, epidermal growth factor receptor and Wnt/b-catenin signaling. PRODH/POX expression is often down-regulated in various tumors, limiting mitochondrial proline utilization to P5C. It is accompanied by increased cytoplasmic level of proline. Proline availability for PRODH/POX-dependent ATP or ROS generation depends on activity of prolidase and utilization of proline in process of collagen biosynthesis. Therefore, Prolidase-PRODH/POX-Collagen Biosynthesis axis may represent potential interface that regulate apoptosis and survival. © 2016 BioFactors, 42(4):341-348, 2016.
authors.affiliation: Department of Medicinal Chemistry, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Zareba
authors.affiliation: Department of Medicinal Chemistry, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Palka
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D053898:Biosynthetic Pathways; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000502:physiology*; D006801:Humans; D011394:Proline Oxidase / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D003094:Collagen; D011394:Proline Oxidase; D004150:Dipeptidases; C022449:proline dipeptidase
keywords: apoptosis; autophagy; collagen metabolism; prolidase; proline dehydrogenase/proline oxidase; signaling