AUTHOR=Patriarca Eduardo J. , Cermola Federica , D’Aniello Cristina , Fico Annalisa , Guardiola Ombretta , De Cesare Dario , Minchiotti Gabriella 

TITLE=The Multifaceted Roles of Proline in Cell Behavior

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.728576

DOI=10.3389/fcell.2021.728576

ISSN=2296-634X

ABSTRACT=<p>Herein, we review the multifaceted roles of proline in cell biology. This peculiar cyclic imino acid is: <bold><italic>(i)</italic></bold> A main precursor of extracellular collagens (the most abundant human proteins), antimicrobial peptides (involved in innate immunity), salivary proteins (astringency, teeth health) and cornifins (skin permeability); <bold><italic>(ii)</italic></bold> an energy source for pathogenic bacteria, protozoan parasites, and metastatic cancer cells, which engage in extracellular-protein degradation to invade their host; <bold><italic>(iii)</italic></bold> an antistress molecule (an osmolyte and chemical chaperone) helpful against various potential harms (UV radiation, drought/salinity, heavy metals, reactive oxygen species); <bold><italic>(iv)</italic></bold> a neural metabotoxin associated with schizophrenia; <bold><italic>(v)</italic></bold> a modulator of cell signaling pathways such as the amino acid stress response and extracellular signal-related kinase pathway; <bold><italic>(vi)</italic></bold> an epigenetic modifier able to promote DNA and histone hypermethylation; <bold><italic>(vii)</italic></bold> an inducer of proliferation of stem and tumor cells; and <bold><italic>(viii)</italic></bold> a modulator of cell morphology and migration/invasiveness. We highlight how proline metabolism impacts beneficial tissue regeneration, but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer.</p>