Poly(ADP-ribosyl)ating pathway regulates development from stem cell niche to longevity control
Abstract
The regulation of poly(ADP-ribose) polymerase, the enzyme responsible for the synthesis of homopolymer ADP-ribose chains on nuclear proteins, has been extensively studied over the last decades for its involvement in tumorigenesis processes. However, the regulation of poly(ADP-ribose) glycohydrolase (PARG), the enzyme responsible for removing this posttranslational modification, has attracted little attention. Here we identified that PARG activity is partly regulated by two phosphorylation sites, ph1 and ph2, in Drosophila. We showed that the disruption of these sites affects the germline stem-cells maintenance/differentiation balance as well as embryonic and larval development, but also the synchronization of egg production with the availability of a calorically sufficient food source. Moreover, these PARG phosphorylation sites play an essential role in the control of fly survivability from larvae to adults. We also showed that PARG is phosphorylated by casein kinase 2 and that this phosphorylation seems to protect PARG protein against degradation in vivo. Taken together, these results suggest that the regulation of PARG protein activity plays a crucial role in the control of several developmental processes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 23, 2021
- Source ID
- 10.26508/lsa.202101071
Entities
People
- Alexei Tulin
- Elena Kotova
- Guillaume Bordet
Organizations
- Fox Chase Cancer Center
- National Science Foundation
- United States Department of Defense
- University of North Dakota