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Wang, P.Y., Lin, W.C., Tsai, Y.C., Cheng, M.L., Lin, Y.H., Tseng, S.H., Chakraborty, A., Pai, L.M. (2015). Regulation of CTP Synthase Filament Formation During DNA Endoreplication in Drosophila.  Genetics 201(4): 1511--1523.
FlyBase ID
FBrf0230390
Publication Type
Research paper
Abstract

CTP synthase (CTPsyn) plays an essential role in DNA, RNA, and lipid synthesis. Recent studies in bacteria, yeast, and Drosophila all reveal a polymeric CTPsyn structure, which dynamically regulates its enzymatic activity. However, the molecular mechanism underlying the formation of CTPsyn polymers is not completely understood. In this study, we found that reversible ubiquitination regulates the dynamic assembly of the filamentous structures of Drosophila CTPsyn. We further determined that the proto-oncogene Cbl, an E3 ubiquitin ligase, controls CTPsyn filament formation in endocycles. While the E3 ligase activity of Cbl is required for CTPsyn filament formation, Cbl does not affect the protein levels of CTPsyn. It remains unclear whether the regulation of CTPsyn filaments by Cbl is through direct ubiquitination of CTPsyn. In the absence of Cbl or with knockdown of CTPsyn, the progression of the endocycle-associated S phase was impaired. Furthermore, overexpression of wild-type, but not enzymatically inactive CTPsyn, rescued the endocycle defect in Cbl mutant cells. Together, these results suggest that Cbl influences the nucleotide pool balance and controls CTPsyn filament formation in endocycles. This study links Cbl-mediated ubiquitination to the polymerization of a metabolic enzyme and reveals a role for Cbl in endocycles during Drosophila development.

PubMed ID
PubMed Central ID
PMC4676535 (PMC) (EuropePMC)
Related Publication(s)
Note

Ubiquitination and filamentous structure of cytidine triphosphate synthase.
Pai et al., 2016, Fly 10(3): 108--114 [FBrf0232910]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genetics
    Title
    Genetics
    Publication Year
    1916-
    ISBN/ISSN
    0016-6731
    Data From Reference