Kremen1-induced cell death is regulated by homo- and heterodimerization.

ABSTRACT: In multicellular organisms, cell death pathways allow the removal of abnormal or unwanted cells. Their dysregulation can lead either to excessive elimination or to inappropriate cell survival. Evolutionary constraints ensure that such pathways are strictly regulated in order to restrain their activation to the appropriate context. We have previously shown that the transmembrane receptor Kremen1 behaves as a dependence receptor, triggering cell death unless bound to its ligand Dickkopf1. In this study, we reveal that Kremen1 apoptotic signaling requires homodimerization of the receptor. Dickkopf1 binding inhibits Kremen1 multimerization and alleviates cell death, whereas forced dimerization increases apoptotic signaling. Furthermore, we show that Kremen2, a paralog of Kremen1, which bears n

SUBMITTER: Sumia I 

PROVIDER: S-EPMC6494814 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature