Related Experiment Video

Updated: Dec 29, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.4K

Cyclin D degradation by E3 ligases in cancer progression and treatment

Shuo Qie1, J Alan Diehl1

  • 1Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Seminars in Cancer Biology
|February 2, 2020
PubMed

Insights

D-type cyclins regulate cell growth by controlling cell cycle progression. Their overexpression in tumors, often due to UPS dysfunction, presents therapeutic opportunities.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • D-type cyclins (D1, D2, D3) are key regulators of the cell cycle.
  • They form complexes with CDK4/6, phosphorylating Rb to promote G1 to S phase transition.
  • Dysregulated D-cyclin accumulation is common in human cancers.

Purpose of the Study:

  • To review the clinicopathological significance of D-type cyclins.
  • To explore the role of the Ubiquitin-Proteasome System (UPS) in D-cyclin overexpression.
  • To discuss therapeutic strategies targeting D-cyclin pathways.

Main Methods:

  • Literature review of D-cyclin function and dysregulation.
  • Analysis of mechanisms contributing to D-cyclin overexpression.
  • Examination of therapeutic approaches targeting D-cyclin machinery.

Main Results:

  • D-cyclins act as mitogenic sensors linking growth signals to cell cycle progression.
  • Overexpression results from gene amplification, altered transcription/translation, reduced microRNAs, and impaired UPS degradation.
  • UPS dysregulation is a significant contributor to elevated D-cyclin levels.

Conclusions:

  • D-cyclins are critical in cell cycle control and cancer development.
  • Targeting UPS-mediated degradation of D-cyclins offers a promising therapeutic avenue.
  • Understanding D-cyclin dysregulation is vital for developing novel cancer treatments.
Keywords:
CancerD cyclinE3 ubiquitin ligaseProtein degradation

More Related Videos

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations10:54

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

Published on: September 17, 2012

10.9K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.7K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.4K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
133.3K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.2K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K
Regulated Protein Degradation02:58

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.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.6K