Related Experiment Video

Updated: Jul 6, 2026

The use of SC1 (Pluripotin) to Support mESC Self-renewal in the Absence of LIF
05:58

The use of SC1 (Pluripotin) to Support mESC Self-renewal in the Absence of LIF

Published on: November 18, 2009

The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans

M X Gao1, E H Liao, B Yu

  • 1Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada.

Cell Death and Differentiation
|March 15, 2008
PubMed

Insights

The SCF(FSN-1) E3 ubiquitin ligase negatively regulates CEP-1/p53-dependent germ cell apoptosis in response to DNA damage. This pathway is crucial for maintaining genomic stability and preventing uncontrolled cell proliferation.

Area of Science:

  • Cellular and Molecular Biology
  • Genetics and Genomics
  • Developmental Biology

Background:

  • The p53 tumor suppressor pathway is a critical regulator of cellular responses to DNA damage, including apoptosis.
  • In the nematode Caenorhabditis elegans, the p53 homolog CEP-1 orchestrates germ cell apoptosis following genotoxic stress.
  • Understanding the regulatory mechanisms governing CEP-1 activity is essential for comprehending DNA damage response pathways.

Purpose of the Study:

  • To elucidate the regulatory network controlling CEP-1-dependent germ cell apoptosis in response to DNA damage.
  • To identify novel components involved in the negative regulation of this crucial cellular process.
  • To investigate the role of the SCF (Skp1/cullin/F-box) E3 ubiquitin ligase complex in modulating CEP-1 activity.

Main Methods:

  • Conducted an RNA interference (RNAi) screen in C. elegans to identify genes regulating germ cell apoptosis.
  • Utilized the DNA-alkylating agent N-ethyl-N-nitrosourea (ENU) to induce genotoxic stress.
  • Employed genetic analysis, including loss-of-function mutations and epistasis experiments, to dissect pathway interactions.
  • Assessed CEP-1 transcriptional activity, phosphorylation status, and protein levels in response to genetic perturbations.

Main Results:

  • Identified components of the neddylation pathway and the SCF E3 ubiquitin ligase complex as negative regulators of CEP-1-dependent germ cell apoptosis.
  • Demonstrated that cul-1, skr-1, rbx-1, and rpm-1 negatively regulate this process.
  • Showed that the F-box protein FSN-1, as part of an SCF(FSN-1) E3 ubiquitin ligase, acts as a negative regulator.
  • Found that fsn-1 mutants exhibit hypersensitivity to ENU-induced germline apoptosis, which is suppressed by cep-1 loss-of-function.
  • Observed elevated CEP-1 transcriptional activity, phosphorylation, and protein levels in fsn-1 mutants post-ENU treatment.

Conclusions:

  • The SCF(FSN-1) E3 ubiquitin ligase complex plays a novel and significant role in negatively regulating CEP-1-dependent germ cell apoptosis.
  • This regulatory mechanism is crucial for controlling the extent of apoptosis in response to DNA damage, thereby maintaining genomic integrity.
  • The findings provide new insights into the complex interplay between ubiquitin ligases and the p53/CEP-1 pathway in stress response.

More Related Videos

Detecting Protein Subcellular Localization by Green Fluorescence Protein Tagging and 4',6-Diamidino-2-phenylindole Staining in Caenorhabditis elegans09:36

Detecting Protein Subcellular Localization by Green Fluorescence Protein Tagging and 4',6-Diamidino-2-phenylindole Staining in Caenorhabditis elegans

Published on: July 30, 2018

Computational Analysis of the Caenorhabditis elegans Germline to Study the Distribution of Nuclei, Proteins, and the Cytoskeleton08:01

Computational Analysis of the Caenorhabditis elegans Germline to Study the Distribution of Nuclei, Proteins, and the Cytoskeleton

Published on: April 19, 2018

Related Concept Videos

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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
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...