Reference: Örd M, et al. (2019) Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle. Mol Cell 75(1):76-89.e3

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Abstract


Cyclin-dependent kinases (CDKs) coordinate hundreds of molecular events during the cell cycle. Multiple cyclins are involved, but the global role of cyclin-specific phosphorylation has remained unsolved. We uncovered a cyclin docking motif, LxF, that mediates binding of replication factor CDC6 to mitotic cyclin. This interaction leads to phospho-adaptor CKS1-mediated inhibition of M-CDK to facilitate CDC6 accumulation and sequestration in mitosis. The LxF motif and CKS1 also mediate the mutual inhibition between M-CDK and the tyrosine kinase SWE1. Additionally, the LxF motif is critical for targeting M-CDK to phosphorylate several mitotic regulators; for example, SPO12 is targeted via LxF to release the phosphatase CDC14. The results complete the full set of G1, S, and M-CDK docking mechanisms and outline the unified role of cyclin specificity and CDK activity thresholds. Cooperation of cyclin and CKS1 docking creates a variety of CDK thresholds and switching orders, including combinations of last in, first out (LIFO) and first in, first out (FIFO) ordering.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Örd M, Venta R, Möll K, Valk E, Loog M
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