A novel landscape of nuclear human CDK2 substrates revealed by in situ phosphorylation

Yong Chi, John H. Carter, Jherek Swanger, Alexander V. Mazin, Robert L. Moritz, Bruce E. Clurman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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, ∼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.

Original languageEnglish (US)
Article numbereaaz9899
JournalScience Advances
Volume6
Issue number16
DOIs
StatePublished - Apr 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

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