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Related Concept Videos

Centrioles and Centrosomes01:13

Centrioles and Centrosomes

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Most animal cells comprise a pair of centrioles together called a centrosome. The cell duplicates its centrosome and contains two centrosomes side-by-side, which begin to move apart during the prophase. As the centrosomes migrate to two different sides of the cell, microtubules start extending from each centrosome toward the other end. The mitotic spindle is composed of the centrosomes and their emerging microtubules.
Near the end of the prophase, also called late prophase or...
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Centrosome Duplication02:25

Centrosome Duplication

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The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
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Abnormal Proliferation02:23

Abnormal Proliferation

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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...
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Inflammatory Response01:28

Inflammatory Response

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An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
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EPS and iPS Cells in Disease Research01:21

EPS and iPS Cells in Disease Research

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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Related Experiment Video

Updated: Jul 20, 2025

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes
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Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes

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Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.

Irmina Garcia-Carpio1, Vincent Z Braun1, Elias S Weiler1

  • 1Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

The EMBO Journal
|August 2, 2023
PubMed
Summary

Extra centrosomes, common in cancer, trigger sterile inflammation and activate NF-κB signaling via the PIDDosome complex. This enhances cancer cell immunogenicity and susceptibility to natural killer cell attacks.

Keywords:
NF-κBPIDDosomecentrosomeimmunosurveillancesterile inflammation

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Area of Science:

  • Cell Biology
  • Immunology
  • Cancer Biology

Background:

  • Unscheduled polyploidization and centrosome amplification are linked to tissue dysfunction and cancer.
  • Supernumerary centrosomes are observed in tumors, correlating with poor prognosis.
  • Extra centrosomes can initially activate p53, inducing cell cycle arrest, but their broader signaling roles are unclear.

Purpose of the Study:

  • To investigate the signaling pathways activated by extra centrosomes.
  • To determine the role of centrosomes in innate immune responses.
  • To explore the therapeutic potential of targeting centrosome-induced signaling.

Main Methods:

  • Analysis of cells with unscheduled polyploidization or aberrant centriole biogenesis.
  • Investigation of NF-κB signaling activation.
  • Study of the NEMO-PIDDosome complex (PIDD1, RIPK1, NEMO/IKKγ).
  • Assessment of chemokine and cytokine profiles.
  • Macrophage polarization assays.
  • Evaluation of cancer cell immunogenicity and NK-cell susceptibility.

Main Results:

  • Extra centrosomes activate NF-κB signaling and induce sterile inflammation.
  • This signaling is dependent on the NEMO-PIDDosome complex.
  • Supernumerary centrosomes promote a paracrine chemokine and cytokine profile, polarizing macrophages.
  • Extra centrosomes increase cancer cell immunogenicity and NK-cell mediated killing.

Conclusions:

  • The PIDDosome complex acts as a crucial mediator linking extra centrosomes to both cell cycle control (p53) and innate immunity (NF-κB).
  • Extra centrosomes can enhance anti-tumor immunity by increasing cancer cell immunogenicity.
  • Targeting centrosome-associated signaling pathways may offer novel therapeutic strategies for cancer.