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Regulated Protein Degradation

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Positive Regulator Molecules

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Anaphase Promoting Complex

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Negative Regulator Molecules

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Related Experiment Video

Updated: Jul 11, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Multiple cullin-associated E3 ligases regulate cyclin D1 protein stability.

Ke Lu¹, Ming Zhang², Guizheng Wei¹

¹Research Center for Computer-aided Drug Discovery, Chinese Academy of Sciences, Shenzhen, China.

|November 9, 2023

Summary

This summary is machine-generated.

New E3 ligases, Keap1, DDB2, and WSB2, control cyclin D1 stability and cell cycle progression by regulating its degradation. This finding offers new insights into cancer-related cell cycle regulation.

Keywords:

DDB2 Keap1 Rbx1 WSB2 cell biology cullin-associated E3 ligase cyclin D1 human

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Last Updated: Jul 11, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

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Published on: May 3, 2018

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

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Published on: September 17, 2012

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Area of Science:

Molecular Biology
Cell Biology
Oncology

Background:

Cyclin D1 is a crucial regulator of cell cycle G1/S transition and is often upregulated in cancers.
Its stability is primarily regulated by ubiquitination/proteasome degradation, influenced by phosphorylation.
Known regulators include cullin-associated F-box E3 ligases, but others may exist.

Purpose of the Study:

To identify novel cullin-associated E3 ligases involved in regulating cyclin D1 protein stability.
To investigate the role of these E3 ligases in cell cycle control and proliferation.

Main Methods:

Screened an siRNA library targeting 154 ligase subunits (F-box, SOCS, BTB, DDB proteins).
Assessed E3 ligase interaction with cyclin D1.
Analyzed ubiquitination, proteasome degradation, and phosphorylation-dependent regulation of cyclin D1.
Evaluated effects on cell cycle progression and proliferation.

Main Results:

Identified Keap1, DDB2, and WSB2 as novel cullin-associated E3 ligases regulating cyclin D1.
Demonstrated that these E3 ligases interact with cyclin D1, promoting its ubiquitination and proteasome degradation in a phosphorylation-dependent manner.
Showed that these E3 ligases impact cell cycle progression and proliferation via cyclin D1 stability.

Conclusions:

Multiple cullin-associated E3 ligases, including Keap1, DDB2, and WSB2, play significant roles in regulating cyclin D1 protein stability.
These findings expand our understanding of cyclin D1 regulation and its implications in cell cycle control and cancer.