What is it about?
We reveal that the balance of poly(A) binding protein PABP-2/PABPN1 and UBR-5 E3 ligase activity levels control the cellular transition out of stemness into differentiation. Elevated levels of PABP-2 prolongs stem fate properties. During cell fate transition, UBR-5 E3 ligase degrades PABP-2 to promote cellular differentiation. We further show that the balance of UBR-5 and PABP-2 levels control extent of motility during aging.
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Why is it important?
Understanding how stemness during development impacts tissue integrity during aging remains a major area of study with limited understanding. Our work provides insights into how a stem promoting program mediated by the poly(A) binding protein PABP-2/PABPN1 is controlled by the animal-specific UBR-5 E3 ligase.
Perspectives
When we first observed the ubr-5 mutant phenotype where descendant cells retained expression of stem markers despite exiting the stem program, we said "Hey, this is like the song Hotel California... you can check out any time you like but you can never leave." Working to understand the connections of proteostasis to tissue integrity in aging and the tradeoff of developmental stemness with healthspan during aging remain areas with so much left to learn.
Associate Professor Benjamin P. Weaver
UT Southwestern Medical Center
Read the Original
This page is a summary of: UBR-5 and UBE2D mediate timely exit from stem fate via destabilization of poly(A)-binding protein PABP-2 in cell state transition, Proceedings of the National Academy of Sciences, October 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2407561121.
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