Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer

IF 12.1 1区 医学 Q1 ONCOLOGY Seminars in cancer biology Pub Date : 2024-01-01 DOI:10.1016/j.semcancer.2023.12.002
Dorian V. Ziegler , Kanishka Parashar , Lluis Fajas
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Abstract

CDK4, along with its regulatory subunit, cyclin D, drives the transition from G1 to S phase, during which DNA replication and metabolic activation occur. In this canonical pathway, CDK4 is essentially a transcriptional regulator that acts through phosphorylation of retinoblastoma protein (RB) and subsequent activation of the transcription factor E2F, ultimately triggering the expression of genes involved in DNA synthesis and cell cycle progression to S phase. In this review, we focus on the newly reported functions of CDK4, which go beyond direct regulation of the cell cycle. In particular, we describe the extranuclear roles of CDK4, including its roles in the regulation of metabolism, cell fate, cell dynamics and the tumor microenvironment. We describe direct phosphorylation targets of CDK4 and decipher how CDK4 influences these physiological processes in the context of cancer.

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细胞周期调控之外:CDK4 在癌症中的多重功能。
CDK4 及其调节亚基细胞周期蛋白 D 驱动着 DNA 复制和新陈代谢激活从 G1 期向 S 期过渡。在这一典型途径中,CDK4 本质上是一种转录调节因子,它通过磷酸化视网膜母细胞瘤蛋白(RB)和随后激活转录因子 E2F 发挥作用,最终引发参与 DNA 合成和细胞周期进入 S 期的基因表达。在这篇综述中,我们将重点讨论新近报道的 CDK4 功能,这些功能超出了对细胞周期的直接调控。我们特别描述了 CDK4 的核外作用,包括其在调节新陈代谢、细胞命运、细胞动力学和肿瘤微环境方面的作用。我们描述了 CDK4 的直接磷酸化靶点,并解读了 CDK4 如何在癌症背景下影响这些生理过程。
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来源期刊
Seminars in cancer biology
Seminars in cancer biology 医学-肿瘤学
CiteScore
26.80
自引率
4.10%
发文量
347
审稿时长
15.1 weeks
期刊介绍: Seminars in Cancer Biology (YSCBI) is a specialized review journal that focuses on the field of molecular oncology. Its primary objective is to keep scientists up-to-date with the latest developments in this field. The journal adopts a thematic approach, dedicating each issue to an important topic of interest to cancer biologists. These topics cover a range of research areas, including the underlying genetic and molecular causes of cellular transformation and cancer, as well as the molecular basis of potential therapies. To ensure the highest quality and expertise, every issue is supervised by a guest editor or editors who are internationally recognized experts in the respective field. Each issue features approximately eight to twelve authoritative invited reviews that cover various aspects of the chosen subject area. The ultimate goal of each issue of YSCBI is to offer a cohesive, easily comprehensible, and engaging overview of the selected topic. The journal strives to provide scientists with a coordinated and lively examination of the latest developments in the field of molecular oncology.
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