Defective in mitotic arrest 1 (Dma1) ubiquitin ligase controls G1 cyclin degradation
Author
Hernández-Ortega, Sara
Ricco Pacheco, Natalia
Ramírez, Sara
Casals i Farré, Núria
Jiménez, Javier
Isasa, Marta
Crosas, Bernat
Clotet Erra, Josep
Publication date
2013-02ISSN
0021-9258
Abstract
Progression through the G1 phase of the cell cycle is controlled by diverse cyclin-dependent kinases (CDKs) that might be associated to numerous cyclin isoforms. Given such complexity, regulation of cyclin degradation should be crucial for coordinating progression through the cell cycle. In Saccharomyces cerevisiae, SCF is the only E3 ligase known to date to be involved in G1 cyclin degradation. Here, we report the design of a genetic screening that uncovered Dma1 as another E3 ligase that targets G1 cyclins in yeast. We show that the cyclin Pcl1 is ubiquitinated in vitro and in vivo by Dma1, and accordingly, is stabilized in dma1 mutants. We demonstrate that Pcl1 must be phosphorylated by its own CDK to efficiently interact with Dma1 and undergo degradation. A nonphosphorylatable version of Pcl1 accumulates throughout the cell cycle, demonstrating the physiological relevance of the proposed mechanism. Finally, we present evidence that the levels of Pcl1 and Cln2 are independently controlled in response to nutrient availability. This new previously unknown mechanism for G1 cyclin degradation that we report here could help elucidate the specific roles of the redundant CDK-cyclin complexes in G1.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Fisiologia
Cribatge genètic
Fisiología
Genes -- Despistaje
Physiology
Genetic screening
Pages
11
Publisher
American Society for Biochemistry and Molecular Biology
Collection
288; 7
Is part of
Journal of Biological Chemistry
Citation
Hernández-Ortega, Sara; Bru, Samuel; Ricco, Natalia [et al.]. Defective in mitotic arrest 1 (Dma1) ubiquitin ligase controls G1 cyclin degradation. Journal of Biological Chemistry, 2013, 288(7), p. 4704-4714. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925820462738?via%3Dihub>. Fecha de acceso: 21 abr. 2021. DOI: 10.1074/jbc.M112.426593
This item appears in the following Collection(s)
- Ciències de la Salut [745]
Rights
Under a Creative Commons license
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/