Related Experiment Video

Updated: Jun 6, 2026

High Content Screening in Neurodegenerative Diseases
13:32

High Content Screening in Neurodegenerative Diseases

Published on: January 6, 2012

DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB

R Sean McNally1, Beckley K Davis, Casey M Clements

  • 1Department of Microbiology-Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.

The Journal of Biological Chemistry
|November 25, 2010
PubMed

Insights

DJ-1 protein enhances cancer cell survival by inhibiting Cezanne, a deubiquitination enzyme. This interaction impacts NF-κB signaling, IL-8, and ICAM-1, offering new insights into cancer progression and Parkinson disease.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • DJ-1 (Park7) expression correlates with reduced cancer cell death and poor prognosis.
  • Loss of DJ-1 function is linked to neuronal death in Parkinson disease.
  • DJ-1's role in cell survival is complex and warrants further investigation.

Purpose of the Study:

  • To elucidate a novel pathway by which DJ-1 modulates cell survival.
  • To identify DJ-1 interacting partners involved in cell survival regulation.
  • To investigate the functional consequences of DJ-1 and its interacting partners on key cellular pathways.

Main Methods:

  • Mass spectrometry to identify DJ-1 interacting proteins.
  • Co-immunoprecipitation to confirm DJ-1/Cezanne interaction.
  • Microarray profiling and analysis of mouse primary cells to assess gene expression changes.

Main Results:

  • DJ-1 interacts with Cezanne (OTUD7B), a deubiquitination enzyme that inhibits NF-κB.
  • DJ-1 binding inhibits Cezanne's deubiquitinating activity, leading to enhanced NF-κB nuclear translocation and cell survival.
  • DJ-1 and Cezanne oppositely regulate IL-8 and ICAM-1 expression, impacting angiogenesis and tumor progression.

Conclusions:

  • DJ-1 controls cell survival and potentially tumor progression through its interaction with Cezanne.
  • This novel pathway involving DJ-1, Cezanne, and NF-κB provides new therapeutic targets for cancer.
  • Understanding DJ-1's dual role in cancer and Parkinson disease is crucial for developing effective treatments.

More Related Videos

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

Related Concept Videos

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.
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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.