Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle

Deota, S.; Rathnachalam, S.; Namrata, K.; Boob, M.; Fulzele, A.; S, R.; Ganguli, S.; Balaji, C.; Kaypee, S.; Vishwakarma, K. K.; Kundu, T. K.; Bhandari, R.; Gozalez de Peredo, A.; Mishra, M.; Venkatramani, R.; Kolthur-Seetharam, U.

doi:10.1101/420000

bioRxiv · 10.1101/420000

Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle

Deota, S.·Rathnachalam, S.·Namrata, K.·Boob, M.·Fulzele, A.·S, R.·Ganguli, S.·Balaji, C.·Kaypee, S.·Vishwakarma, K. K.·Kundu, T. K.·Bhandari, R.·Gozalez de Peredo, A.·Mishra, M.·Venkatramani, R.·Kolthur-Seetharam, U.

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Abstract

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.

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Deota, S., Rathnachalam, S., Namrata, K., Boob, M., Fulzele, A., S, R., Ganguli, S., Balaji, C., Kaypee, S., Vishwakarma, K. K., Kundu, T. K., Bhandari, R., Gozalez de Peredo, A., Mishra, M., Venkatramani, R., Kolthur-Seetharam, U.. 2018-09-17. Deacetylation of catalytic lysine in CDK1 is essential for Cyclin-B binding and cell cycle. https://doi.org/10.1101/420000

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