Journal article
A novel landscape of nuclear human CDK2 substrates revealed by in situ phosphorylation
SCIENCE ADVANCES, v 6(16), eaaz9899
Apr 2020
PMID: 32494624
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cyclin-dependent kinase 2 (CDK2) controls cell division and is central to oncogenic signaling. We used an in situ approach to identify CDK2 substrates within nuclei isolated from cells expressing CDK2 engineered to use adenosine 5'-triphosphate analogs. We identified 117 candidate substrates, similar to 40% of which are known CDK substrates. Previously unknown candidates were validated to be CDK2 substrates, including LSD1, DOT1L, and Rad54. The identification of many chromatin-associated proteins may have been facilitated by labeling conditions that preserved nuclear architecture and physiologic CDK2 regulation by endogenous cyclins. Candidate substrates include proteins that regulate histone modifications, chromatin, transcription, and RNA/DNA metabolism. Many of these proteins also coexist in multi-protein complexes, including epigenetic regulators, that may provide new links between cell division and other cellular processes mediated by CDK2. In situ phosphorylation thus revealed candidate substrates with a high validation rate and should be readily applicable to other nuclear kinases.
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Details
- Title
- A novel landscape of nuclear human CDK2 substrates revealed by in situ phosphorylation
- Publication Details
- SCIENCE ADVANCES, v 6(16), eaaz9899
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE; WASHINGTON
- Grant note
- This publication was supported by grants 1R01CA193808 (B.E.C.), CA188347 (A. V.M.), and P30CA056036 and Cancer Center Support grant 2P30CA015704. This work was funded in part by the National Institutes of Health, National Institute of General Medical Sciences grants: R01GM087221 (R.L.M).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000528276800043
- Scopus ID
- 2-s2.0-85083628400
- Other Identifier
- 991021860671604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology