Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle

被引：52

作者：

Ord, Mihkel ^{[1
]}

Venta, Rainis ^{[1
]}

Moll, Kaidi ^{[1
]}

Valk, Ervin ^{[1
]}

Loog, Mart ^{[1
]}

机构：

[1] Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia

来源：

MOLECULAR CELL | 2019年 / 75卷 / 01期

基金：

欧洲研究理事会;

关键词：

S-PHASE; DNA-REPLICATION; MITOTIC CYCLINS; SUBSTRATE PHOSPHORYLATION; SCFCDC4; RECOGNITION; ACTIN CYTOSKELETON; GLOBAL ANALYSIS; SWE1; REGULATION; CDC6; PROTEIN;

D O I：

10.1016/j.molcel.2019.04.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：76 / +

页数：17

共 70 条

[1] Cdc6 degradation requires phosphodegron created by GSK-3 and Cdk1 for SCFCdc4 recognition in Saccharomyces cerevisiae [J].