UBR-5 and UBE2D mediate timely exit from stem fate via destabilization of poly(A)-binding protein PABP-2 in cell state transition.

ABSTRACT: UBR5 E3 ligase has been associated with cancer susceptibility and neuronal integrity, with functions in chromatin regulation and proteostasis. However, the functions of ubr5 within animals remain unclear due to lethality in both mammals and flies when disrupted. Using Caenorhabditis elegans, we show that UBR-5 E3 ligase is required for timely exit of stem fate and complete transition into multiple cell type descendants in an ectodermal blast lineage. Animals lacking intact UBR-5 function simultaneously exhibit both stem fate and differentiated fate in the same descendant cells. A functional screen of UBR-5 physical interactors allowed us to identify the UBE2D2/3 E2 conjugase LET-70 working with UBR-5 to exit stem fate. Strikingly, we revealed that another UBR-5 physical inter

SUBMITTER: Calva Moreno JF 

PROVIDER: S-EPMC11513905 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature