Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses
| Autor: | James M. Phang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Senescence senescence Proline Physiology Clinical Biochemistry Biology Biochemistry 03 medical and health sciences Proline dehydrogenase Downregulation and upregulation Neoplasms pyridine nucleotides Proline Oxidase metastasis Humans redox signaling Molecular Biology PI3K/AKT/mTOR pathway General Environmental Science chemistry.chemical_classification Reactive oxygen species Proline oxidase Autophagy Cell Biology Forum Review Articles Cell biology 030104 developmental biology chemistry General Earth and Planetary Sciences Tumor Suppressor Protein p53 resistance to oxidative stress Oxidation-Reduction Reprogramming proline cycle |
| Zdroj: | Antioxidants & Redox Signaling |
| ISSN: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2017.7350 |
| Popis: | Significance: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a tumor protein 53 (P53)-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses. On the biosynthetic side, two well-recognized oncogenes, c-MYC and phosphoinositide 3-kinase (PI3K), markedly upregulate enzymes of proline synthesis; mechanisms affected include augmented redox cycling and maintenance of pyridine nucleotides. The reprogramming has been shown to shift in clonogenesis and/or metastasis. Critical Issues: Although PRODH/POX generates reactive oxygen species (ROS) for signaling, the cellular endpoint is variable and dependent on metabolic context; the switches for these responses remain unknown. On the synthetic side, the enzymes require more complete characterization in various cancers, and demonstration of coupling of proline metabolites to other pathways may require studies of protein–protein interactions, membrane transporters, and shuttles. Future Directions: The proline metabolic axis can serve as a scaffold on which a variety of regulatory mechanisms are integrated. Once understood as a central mechanism in cancer metabolism, proline metabolism may be a good target for adjunctive cancer therapy. |
| Databáze: | OpenAIRE |
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