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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...
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...
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...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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.

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Related Experiment Video

Updated: Jun 26, 2026

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
05:35

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

Restriction of Src activity by Cullin-5.

George S Laszlo1, Jonathan A Cooper

  • 1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Current Biology : CB
|January 17, 2009
PubMed
Summary
This summary is machine-generated.

High levels of active Src protein are degraded, requiring overexpression for cell transformation. Cullin-5 (Cul5) acts as a tumor suppressor by downregulating active Src, limiting its oncogenic effects.

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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Last Updated: Jun 26, 2026

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale
10:50

Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale

Published on: March 14, 2019

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Src is a nonreceptor tyrosine kinase regulating cell functions like proliferation and migration.
  • Normally, Src activity is tightly controlled by phosphatases, but its deregulation drives malignant transformation.
  • The precise levels of mutant Src required for transformation relative to endogenous Src were unclear.

Purpose of the Study:

  • To investigate the quantitative requirements for mutant Src in cell transformation.
  • To identify mechanisms regulating active Src protein levels.
  • To explore the role of Cullin-5 (Cul5) in controlling Src activity and oncogenesis.

Main Methods:

  • Analysis of mutant src mRNA and protein levels.
  • Investigation of ubiquitin-mediated proteolysis of Src.
  • Studies involving Cullin-5 (Cul5) knockout or knockdown.
  • Assessment of protein tyrosine phosphorylation, cell morphology, and growth deregulation.
  • Evaluation of Src-induced tumorigenesis in vivo.

Main Results:

  • Cell transformation necessitates high-level overexpression of mutant src mRNA, partly due to active Src protein degradation.
  • Active Src protein is downregulated by Cullin-5 (Cul5), an E3 ubiquitin ligase component.
  • Cul5 depletion enhances Src-driven transformation and deregulated growth, even at physiological mutant src mRNA levels.
  • Cul5 also suppresses Src-induced tumorigenesis and regulates Src signaling in normal cells.

Conclusions:

  • Active Src protein is subject to degradation, necessitating overexpression for malignant transformation.
  • Cullin-5 (Cul5) functions as a critical regulator, downregulating active Src and its substrates to limit oncogenic signaling.
  • Cul5 represents a novel tumor suppressor mechanism controlling Src activity in both normal and cancerous cells.