Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation.
dc.contributor.author | Salamina, Marco | |
dc.contributor.author | Montefiore, Bailey C | |
dc.contributor.author | Liu, Mengxi | |
dc.contributor.author | Wood, Daniel J | |
dc.contributor.author | Heath, Richard | |
dc.contributor.author | Ault, James R | |
dc.contributor.author | Wang, Lan-Zhen | |
dc.contributor.author | Korolchuk, Svitlana | |
dc.contributor.author | Baslé, Arnaud | |
dc.contributor.author | Pastok, Martyna W | |
dc.contributor.author | Reeks, Judith | |
dc.contributor.author | Tatum, Natalie J | |
dc.contributor.author | Sobott, Frank | |
dc.contributor.author | Arold, Stefan T. | |
dc.contributor.author | Pagano, Michele | |
dc.contributor.author | Noble, Martin E M | |
dc.contributor.author | Endicott, Jane A | |
dc.date.accessioned | 2021-02-03T11:50:24Z | |
dc.date.available | 2021-02-03T11:50:24Z | |
dc.date.issued | 2021-01-10 | |
dc.date.submitted | 2020-10-26 | |
dc.identifier.citation | Salamina, M., Montefiore, B. C., Liu, M., Wood, D. J., Heath, R., Ault, J. R., … Endicott, J. A. (2021). Discriminative SKP2 interactions with CDK-cyclin complexes support a cyclin A-specific role in p27KIP1 degradation. Journal of Molecular Biology, 166795. doi:10.1016/j.jmb.2020.166795 | |
dc.identifier.issn | 0022-2836 | |
dc.identifier.pmid | 33422522 | |
dc.identifier.doi | 10.1016/j.jmb.2020.166795 | |
dc.identifier.doi | 10.1101/2020.10.08.329599 | |
dc.identifier.uri | http://hdl.handle.net/10754/667206 | |
dc.description.abstract | The SCF$^{SKP2}$ ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyclin A can stabilize SKP1-SKP2-CDK2-cyclin A complexes in the absence of CKS1. We identify the SKP2 binding site on cyclin A and demonstrate the site is not present in cyclin B or cyclin E. This site is distinct from but overlapping with features that mediate binding of p27KIP1 and other G1 cyclin regulators to cyclin A. We propose that the capacity of SKP2 to engage with CDK2-cyclin A by more than one structural mechanism provides a way to fine tune the degradation of p27KIP1 and distinguishes cyclin A from other G1 cyclins to ensure orderly cell cycle progression. | |
dc.description.sponsorship | X-ray crystallography and SAXS was carried out with the support of Diamond Light Source on beamlines I04-1 (proposal MX13587) and BL21 (sm16970-2) respectively. We thank N. Schueller, M. Hoellerer and H. Ruddick (University of Oxford) for preparation and initial construct characterization and for assistance with preparation of the mutants; K. Cole, M. Martin, C. Jennings and A. Wittner for assistance with the SEC, ITC, mass spectrometry and cell-based studies respectively. H. Waller and O. Davies provided invaluable assistance to carry out the ITC and SEC-MALLS. B. Hao (U. Connecticut) for providing the SKP1-SKP2 co-expression plasmid. This research was supported by the Wellcome Trust (Grant Reference 063551); MRC (Grant References G0901526 and MR/N009738/1), Cancer Research UK (Grant Reference C2115/A21421), Newcastle Cancer Centre and the JGW Patterson Foundation and the BBSRC (Grant Reference BB/M012573/1). The LEAP sample handling robot used in the HDX-MS work was a kind donation from Waters UK. M.P. is an Investigator with the Howard Hughes Medical Institute and funded by grants from the National Institutes of Health to M.P. (GM136250 and CA76584). Research by S.A. reported in this publication was supported by the King Abdullah University of Science and Technology (KAUST). | |
dc.publisher | Elsevier BV | |
dc.relation.url | https://linkinghub.elsevier.com/retrieve/pii/S0022283620307208 | |
dc.rights | This is an open access article under the CC BY license. | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation. | |
dc.type | Article | |
dc.contributor.department | Bioscience Program | |
dc.contributor.department | Computational Bioscience Research Center (CBRC) | |
dc.contributor.department | Biological and Environmental Sciences and Engineering (BESE) Division | |
dc.identifier.journal | Journal of molecular biology | |
dc.eprint.version | Publisher's Version/PDF | |
dc.contributor.institution | Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Paul O’Gorman Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. | |
dc.contributor.institution | Department of Biochemistry and Molecular Pharmacology, Perlmutter NYU Cancer Center, New York University Grossman School of Medicine, and Howard Hughes Medical Institute, The Alexandria Center of Life Science, East Tower, 450 E, 29th Street, New York, NY 10016, USA. | |
dc.contributor.institution | Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK. | |
dc.contributor.institution | Biosciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. | |
dc.contributor.institution | Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, 34090 Montpellier, France. | |
dc.identifier.pages | 166795 | |
kaust.person | Arold, Stefan T. | |
dc.date.accepted | 2020-12-28 | |
refterms.dateFOA | 2021-02-03T11:51:42Z |
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