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The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression

Journal

Publisher

MDPI
DOI: 10.3390/ijms22115754

Keywords

cell cycle regulation; CDKs; cyclins; CKIs; UPS; E3 ubiquitin ligases; Deubiquitinases (DUBs)

Funding

  1. Natural Science Foundation Project of CQ CSTC [cstc2020jcyj-msxmX0154]
  2. National Natural Science Foundation of China [31571454]

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The paragraph explains how the cell cycle is regulated by the division of cellular components and the activation of cyclin-dependent kinases. The ubiquitin-proteasome system plays a crucial role in regulating cell proliferation, genomic stability, and cancer occurrence through recognition and modification of key proteins in the cell cycle machinery.
The cell cycle is a collection of events by which cellular components such as genetic materials and cytoplasmic components are accurately divided into two daughter cells. The cell cycle transition is primarily driven by the activation of cyclin-dependent kinases (CDKs), which activities are regulated by the ubiquitin-mediated proteolysis of key regulators such as cyclins, CDK inhibitors (CKIs), other kinases and phosphatases. Thus, the ubiquitin-proteasome system (UPS) plays a pivotal role in the regulation of the cell cycle progression via recognition, interaction, and ubiquitination or deubiquitination of key proteins. The illegitimate degradation of tumor suppressor or abnormally high accumulation of oncoproteins often results in deregulation of cell proliferation, genomic instability, and cancer occurrence. In this review, we demonstrate the diversity and complexity of the regulation of UPS machinery of the cell cycle. A profound understanding of the ubiquitination machinery will provide new insights into the regulation of the cell cycle transition, cancer treatment, and the development of anti-cancer drugs.

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