PT  - JOURNAL ARTICLE
AU  - Shaunak Deota
AU  - Sivasudhan Rathnachalam
AU  - Kanojia Namrata
AU  - Mayank Boob
AU  - Amit Fulzele
AU  - S Radhika
AU  - Shubhra Ganguli
AU  - Chinthapalli Balaji
AU  - Stephanie Kaypee
AU  - Krishna Kant Vishwakarma
AU  - Tapas Kumar Kundu
AU  - Rashna Bhandari
AU  - Anne Gonzalez de Peredo
AU  - Mithilesh Mishra
AU  - Ravindra Venkatramani
AU  - Ullas Kolthur-Seetharam
TI  - Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle
AID  - 10.1101/420000
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 420000
4099  - http://biorxiv.org/content/early/2018/09/20/420000.short
4100  - http://biorxiv.org/content/early/2018/09/20/420000.full
AB  - Cyclin-dependent-kinases (CDKs) are essential for cell cycle progression. While dependence of CDK activity on Cyclin levels is established, molecular mechanisms that regulate their binding are less studied. Here, we show that CDKl:Cyclin-B interactions are regulated by acetylation, which was hitherto unknown. We demonstrate that cell cycle dependent acetylation of the evolutionarily conserved catalytic lysine in CDK1 or eliminating its charge state abrogates Cyclin-B binding. Opposing activities of SIRT1 and P300 regulate acetylation, which marks a reserved pool of CDK1. Our high resolution structural analyses into the formation of kinase competent CDK1: Cyclin-B complex have unveiled long-range effects of catalytic lysine in configuring the CDK1 interface for Cyclin-B binding. Cells expressing acetylation mimic mutant of Cdc2 in yeast are arrested in G2 and fail to divide. Thus, by illustrating cell cycle dependent deacetylation as a determinant of CDK1:Cyclin-B interaction, our results redefine the current model of CDK1 activation and cell cycle progression.