Altered pattern of Cul-1 protein expression and neddylation in human lung tumours: relationships with CAND1 and

Related Experiment Video

Updated: Jul 11, 2026

Genome-Wide Mapping of Histone Modifications and Transcription Factor Binding Sites in Neuroendocrine Small Cell Lung Cancer Cell Lines Using CUT&RUN
11:50

Genome-Wide Mapping of Histone Modifications and Transcription Factor Binding Sites in Neuroendocrine Small Cell Lung Cancer Cell Lines Using CUT&RUN

Published on: April 3, 2026

C Salon1, E Brambilla, C Brambilla

  • 1Equipe Bases Moléculaires de la Progression des Cancers du Poumon, Centre de Recherche INSERM U823, Institut Albert Bonniot, 38706 La Tronche Cedex, France.

The Journal of Pathology
|September 8, 2007
PubMed

Insights

Cul-1 protein, crucial for cell cycle control, is upregulated in 40% of lung tumors. This upregulation correlates with decreased cyclin E, suggesting a protective role against excessive cell growth in lung cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The Cul-1 protein is a key scaffold for SCF complexes, essential for proteasomal degradation of cell cycle regulators.
  • Aberrant SCF component expression is implicated in tumorigenesis, but Cul-1 expression in human tumors remains uncharacterized.

Purpose of the Study:

  • To investigate the expression status of Cul-1 in human lung carcinomas.
  • To explore the correlation between Cul-1 expression, proliferation markers, and key cell cycle proteins.

Main Methods:

  • Immunohistochemistry was employed to analyze Cul-1 expression in 128 human lung tumors (NSCLCs and neuroendocrine lung tumors).
  • Correlation analyses were performed with KI67 proliferation index, cyclin E, and CAND1 protein levels.

Main Results:

  • Cul-1 expression is upregulated in 40% of lung tumors compared to normal lung tissue.
  • Increased Cul-1 levels correlate with reduced KI67 proliferation index and decreased cyclin E oncoprotein.
  • Neddylated Cul-1 forms are specifically found in high-grade neuroendocrine tumors, associated with CAND1 downregulation and high cyclin E.

Conclusions:

  • Cul-1 upregulation may act as a tumor-suppressive mechanism by downregulating cyclin E, potentially protecting against hyperproliferation.
  • Alterations in Cul-1 neddylation/deneddylation pathways may contribute to the aggressive nature of high-grade neuroendocrine lung tumors.

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...
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.
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
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 Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...