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Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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The Spindle Assembly Checkpoint02:19

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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
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Long-patch Base Excision Repair01:02

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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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...
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Related Experiment Videos

Fbw7 and Usp28 - enemies and allies.

Lyudmyla Taranets1, Jing Zhu1, Wenshan Xu1

  • 1Comprehensive Cancer Center Mainfranken and Department of Radiation Oncology; University Hospital Würzburg ; Würzburg, Germany.

Molecular & Cellular Oncology
|June 17, 2016
PubMed
Summary

The deubiquitinase Usp28 protein prevents the degradation of oncoproteins like Myc, promoting cancer. Usp28 also inhibits Fbw7 self-ubiquitination, revealing a complex regulatory role in tumor development.

Keywords:
Fbw7SCFUsp28oncogenetumor suppressorubiquitin

Related Experiment Videos

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • The Fbw7 ubiquitin ligase targets oncoproteins such as Myc, Jun, and Notch for degradation.
  • Dysregulation of Fbw7 activity is implicated in various cancers.
  • Usp28 (ubiquitin-specific protease 28) is known to stabilize oncoproteins by counteracting their degradation.

Purpose of the Study:

  • To investigate the role of Usp28 in regulating Fbw7 activity.
  • To elucidate the complex interplay between Usp28 and Fbw7 in tumorigenesis.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Ubiquitination assays to analyze protein turnover.
  • Cellular models to assess tumorigenesis in the intestine.

Main Results:

  • Usp28 antagonizes Fbw7-mediated degradation of key oncoproteins (Myc, Jun, Notch).
  • Usp28 was found to counteract the autocatalytic ubiquitination of Fbw7.
  • This suggests Usp28 influences Fbw7 activity beyond just its substrates.

Conclusions:

  • Usp28 plays a multifaceted role in regulating Fbw7 activity.
  • The interaction between Usp28 and Fbw7 impacts oncoprotein stability and intestinal tumor development.