FBXL2 is a ubiquitin E3 ligase subunit that triggers mitotic arrest

Related Experiment Video

Updated: May 28, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Bill B Chen1, Jennifer R Glasser, Tiffany A Coon

  • 1Department of Medicine, Acute Lung Injury Center of Excellence, The University of Pittsburgh, Pittsburgh, PA, USA. chenb@upmc.edu

Cell Cycle (Georgetown, Tex.)
|October 26, 2011
PubMed

Insights

The SCF (Skip-Cullin1-F-box protein) E3 ligase FBXL2 impairs cell proliferation by degrading cyclin D3. This leads to mitotic arrest and errors in cell division, highlighting FBXL2

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin E3 ligase complexes are crucial for regulating cell division.
  • The SCF (Skip-Cullin1-F-box protein) E3 ligase family plays a role in cell cycle control.

Purpose of the Study:

  • To investigate the role of SCF (FBXL2) in cell proliferation and mitotic progression.
  • To elucidate the mechanism by which SCF (FBXL2) affects cyclin D3 and centrosome function.

Main Methods:

  • Overexpression of FBXL2 in transformed epithelia.
  • RNAi-mediated knockdown of cyclin D3.
  • Immunofluorescence microscopy to assess centrosome localization and spindle organization.
  • Co-immunoprecipitation assays to study protein interactions.

Main Results:

  • SCF (FBXL2) overexpression caused G2/M-phase arrest, supernumerary centrosomes, and tetraploidy.
  • FBXL2 mediated polyubiquitination and degradation of cyclin D3.
  • Knockdown of cyclin D3 mimicked the effects of FBXL2 overexpression.
  • SCF (FBXL2) disrupted cyclin D3 association with centrosomal proteins like Aurora A, Plk4, and CDK11.

Conclusions:

  • SCF (FBXL2) impairs cell proliferation by targeting cyclin D3 for degradation.
  • FBXL2 plays a critical role in maintaining the fidelity of cell division.
  • Dysregulation of SCF (FBXL2) may contribute to genomic instability.

More Related Videos

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes05:34

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes

Published on: July 14, 2023

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

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

Published on: May 14, 2016

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...