ArticleMolecular and cellular biology2013
Fbw7α and Fbw7γ collaborate to shuttle cyclin E1 into the nucleolus for multiubiquitylation.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
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- HHIP protein interactions in lung cells provide insight into COPD pathogenesis.Human molecular genetics · 2025Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
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- The mechanisms of Pin1 as targets for cancer therapy.Frontiers in immunology · 2024Review
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- Nucleolar stress: Friend or foe in cardiac function?Frontiers in cardiovascular medicine · 2022Review
- CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer.Diagnostics (Basel, Switzerland) · 2020Review
- Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.Frontiers in cell and developmental biology · 2020Review
- Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics.Frontiers in cell and developmental biology · 2020Review
- Cul3 regulates cyclin E1 protein abundance via a degron located within the N-terminal region of cyclin E.Journal of cell science · 2019Article
- Article
- Recent advances in SCF ubiquitin ligase complex: Clinical implications.Biochimica et biophysica acta · 2016Review
- Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7 regulates ciliary length.The EMBO journal · 2015Article
- Isoform-specific SCF(Fbw7) ubiquitination mediates differential regulation of PGC-1α.Journal of cellular physiology · 2015Article
- The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A CULLINary ride across the secretory pathway: more than just secretion.Trends in cell biology · 2014Review
- Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locus SREBF1 as a regulator of mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease.Cell & bioscience · 2014Review
- Golgi-associated RhoBTB3 targets cyclin E for ubiquitylation and promotes cell cycle progression.The Journal of cell biology · 2013Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Cyclin E1, an activator of cyclin-dependent kinase 2 (Cdk2) that promotes replicative functions, is normally expressed periodically within the mammalian cell cycle, peaking at the G(1)-S-phase transition. This periodicity is achieved by E2F-dependent transcription in late G(1) and early S phases and by ubiquitin-mediated proteolysis. The ubiquitin ligase that targets phosphorylated cyclin E is SCF(Fbw7) (also known as SCF(Cdc4)), a member of the cullin ring ligase (CRL) family. Fbw7, a substrate adaptor subunit, is expressed as three splice-variant isoforms with different subcellular distributions: Fbw7α is nucleoplasmic but excluded from the nucleolus, Fbw7β is cytoplasmic, and Fbw7γ is nucleolar. Degradation of cyclin E in vivo requires SCF complexes containing Fbw7α and Fbw7γ, respectively. In vitro reconstitution showed that the role of SCF(Fbw7α) in cyclin E degradation, rather than ubiquitylation, is to serve as a cofactor of the prolyl cis-trans isomerase Pin1 in the isomerization of a noncanonical proline-proline bond in the cyclin E phosphodegron. This isomerization is required for subsequent binding and ubiquitylation by SCF(Fbw7γ). Here we show that Pin1-mediated isomerization of the cyclin E phosphodegron and subsequent binding to Fbw7γ drive nucleolar localization of cyclin E, where it is ubiquitylated by SCF(Fbw7γ) prior to its degradation by the proteasome. It is possible that this constitutes a mechanism for rapid inactivation of phosphorylated cyclin E by nucleolar sequestration prior to its multiubiquitylation and degradation.
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