Kumar, A, Gopalswamy, M, Wolf, A et al. (3 more authors) (2018) Phosphorylation-induced unfolding regulates p19(INK4d) during the human cell cycle. Proceedings of the National Academy of Sciences of the United States of America, 115 (13). pp. 3344-3349. ISSN 0027-8424
Abstract
Cell cycle progression is tightly controlled in healthy organisms and often perturbed in human diseases, including, most prominently, many forms of cancers. Cyclin-dependent protein kinases and their inhibitors, such as p19(INK4d), regulate the different stages of the cell cycle. Here, we demonstrate how sequential phosphorylation of p19(INK4d) at two sites first destabilizes and then unfolds the N-terminal half of the protein, which dissociates its cyclin-dependent protein kinase-inhibitory complex and primes p19(INK4d) for cellular degradation. Our results define a structural mechanism by which phosphorylation-induced protein unfolding controls a key step in cell cycle progression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018. This is an author produced version of a paper published in Proceedings of the National Academy of Sciences of the United States of America. In order to comply with the publisher requirements the University does not require the author to sign a nonexclusive licence for this paper. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | cell cycle; p19INK4d; protein unfolding; protein phosphorylation; NMR spectroscopy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Structural Molecular Biology 2 (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Jun 2018 15:10 |
Last Modified: | 12 Sep 2018 00:38 |
Status: | Published |
Publisher: | National Academy of Sciences |
Identification Number: | 10.1073/pnas.1719774115 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:132698 |