AUTHOR=Jemmerson Ronald 

TITLE=Paradoxical Roles of Leucine-Rich α2-Glycoprotein-1 in Cell Death and Survival Modulated by Transforming Growth Factor-Beta 1 and Cytochrome c

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.2021.744908

DOI=10.3389/fcell.2021.744908

ISSN=2296-634X

ABSTRACT=<p>Leucine-rich α<sub>2</sub>-glycoprotein-1 (LRG1) has been shown to impact both apoptosis and cell survival, pleiotropic effects similar to one of its known ligands, transforming growth factor-beta 1 (TGF-β1). Recent studies have given insight into the TGF-β1 signaling pathways involved in LRG1-mediated death versus survival signaling, i.e., canonical or non-canonical. Interaction of LRG1 with another ligand, extracellular cytochrome <italic>c</italic> (Cyt <italic>c</italic>), promotes cell survival, at least for lymphocytes. LRG1 has been shown to bind Cyt <italic>c</italic> with high affinity, higher than it binds TGF-β1, making it sensitive to small changes in the level of extracellular Cyt <italic>c</italic> within a microenvironment that may arise from cell death. Evidence is presented here that LRG1 can bind TGF-β1 and Cyt <italic>c</italic> simultaneously, raising the possibility that the ternary complex may present a signaling module with the net effect of signaling, cell death versus survival, determined by the relative extent to which the LRG1 binding sites are occupied by these two ligands. A possible role for LRG1 should be considered in studies where extracellular effects of TGF-β1 and Cyt <italic>c</italic> have been observed in media supplemented with LRG1-containing serum.</p>