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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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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...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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GTPases and their Regulation02:14

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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
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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.
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Related Experiment Video

Updated: Jan 21, 2026

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay
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Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay

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USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification.

Casey P Nielsen1, Kristin K Jernigan1, Nicole L Diggins2

  • 1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA.

Cell Reports
|July 25, 2019
PubMed
Summary

USP9X and WWP1 control DVL2 ubiquitylation, directing WNT signaling. USP9X promotes canonical WNT, while ubiquitylation activates the WNT-planar cell polarity pathway, impacting cancer therapeutics.

Keywords:
DUB-E3 interactionsE3 ubiquitin ligasesUSP9XWNT signalingWNT-PCP signalingWWP1deubiquitylasesnon-canonical WNT signalingubiquitin rheostat

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Area of Science:

  • Cellular biology
  • Molecular signaling
  • Biochemistry

Background:

  • The WNT signaling network regulates complex cellular processes through distinct pathways.
  • Distinguishing between canonical and noncanonical WNT pathways is crucial but challenging due to shared signaling components.

Purpose of the Study:

  • To investigate the roles of USP9X and WWP1 in regulating DVL2 ubiquitylation.
  • To elucidate how DVL2 ubiquitylation status determines its involvement in canonical WNT versus WNT-planar cell polarity (PCP) pathways.

Main Methods:

  • Investigated the deubiquitylase USP9X and E3 ligase WWP1 activity on DVL2.
  • Analyzed DVL2 ubiquitylation levels and localization under different WNT pathway activations.

Main Results:

  • USP9X deubiquitylation of DVL2 is essential for canonical WNT pathway activation.
  • Increased ubiquitylation of DVL2 correlates with its localization to actin-rich regions and activation of the WNT-PCP pathway.
  • A WWP1-USP9X axis regulates DVL2 ubiquitylation, acting as a switch between WNT pathways.

Conclusions:

  • A novel regulatory mechanism involving a ubiquitin rheostat on DVL2 specifies WNT pathway choice.
  • Targeting USP9X offers potential therapeutic strategies for WNT-pathway-driven human cancers.