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Published on: June 6, 2017
CSN5/Jab1 controls multiple events in the mammalian cell cycle
Akihiro Yoshida1, Noriko Yoneda-Kato, Martina Panattoni
1Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
FEBS Letters
|October 27, 2010
Summary
The COP9 signalosome subunit 5 (CSN5/Jab1) is essential for mammalian cell cycle progression. Its removal halts proliferation, induces senescence, and disrupts cell cycle regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The COP9 signalosome (CSN) complex is vital for mammalian cell proliferation and survival.
- The precise role of CSN in regulating the cell cycle remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of CSN5/Jab1 in mammalian cell cycle control.
- To elucidate the molecular mechanisms by which CSN5/Jab1 influences cell proliferation and survival.
Main Methods:
- Generation of mouse embryonic fibroblasts (MEFs) lacking CSN5/Jab1 using a CRE-lox system.
- Rescue experiments to confirm the essentiality of the JAMM domain of CSN5/Jab1.
- Analysis of neddylation status of cullins, expression of cell cycle regulators (e.g., cyclin E, p53), and cell cycle progression.
Main Results:
- Elimination of CSN5/Jab1 led to cessation of MEF proliferation.
- CSN5/Jab1 deficiency enhanced neddylation of cullins 1 and 4 and altered the expression of key cell cycle factors.
- CSN5/Jab1-deficient cells exhibited inhibited cell cycle progression, p53-independent senescence, and increased ploidy.
Conclusions:
- CSN5/Jab1 plays a critical role in regulating multiple stages of the somatic cell cycle.
- CSN5/Jab1 is essential for preventing cellular senescence and maintaining proper cell cycle progression.
- The JAMM domain of CSN5/Jab1 is crucial for its function in cell cycle control.
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