Cyclin-dependent kinase 4 inhibits the translational repressor 4E-BP1 to promote cap-dependent translation during mitosis–G1 transition

FEBS Letters

article

Dylan C. Mitchell¹  Arya Menon²  Amanda L. Garner¹ 

[1] Program in Chemical Biology, University of Michigan;Department of Medicinal Chemistry, College of Pharmacy, University of Michigan

关键词: 4E-BP1;    cap-dependent translation;    CDK4;    mitosis;   

DOI  :  10.1002/1873-3468.13721

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phosphorylation of translational repressor eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) controls the initiation of capdependent translation, a type of protein synthesis that is frequently upregulated in human diseases such as cancer. Because of its critical cellular function, it is not surprising that multiple kinases can post-translationally modify 4E-BP1 to drive aberrant cap-dependent translation. We recently reported a site-selective chemoproteomic method for uncovering kinase–substrate interactions, and using this approach, we discovered the cyclin-dependent kinase (CDK)4 as a new 4E-BP1 kinase. Herein, we describe our extension of this work and reveal the role of CDK4 in modulating 4E-BP1 activity in the transition from mitosis to G1, thereby demonstrating a novel role for this kinase in cell cycle regulation.

【 授权许可】

Unknown