Related Experiment Video

Updated: Sep 19, 2025

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
09:45

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples

Published on: May 10, 2015

9.8K

OTU deubiquitinases in disease: roles and targeting

Yu Deng1, Pengda Liu1

  • 1Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Trends in Molecular Medicine
|June 17, 2025
PubMed

Insights

Ovarian tumor proteases (OTUs) are key regulators of protein homeostasis. Understanding OTU function and dysregulation offers new therapeutic strategies for diseases like cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Protein homeostasis is crucial for preventing human diseases.
  • Proteasome degradation relies on ubiquitination, regulated by E3 ligases and deubiquitinases (DUBs).
  • The ovarian tumor protease (OTU) family of DUBs specifically cleaves poly-ubiquitin chains, impacting cellular processes.

Purpose of the Study:

  • To review the functions and regulatory mechanisms of OTU deubiquitinases.
  • To explore the association of OTU dysregulation with human diseases, particularly cancer.
  • To summarize current therapeutic strategies targeting OTUs.

Main Methods:

  • Literature review of current research on OTU proteases.
  • Analysis of OTU family functions, regulation, and disease links.
  • Examination of therapeutic approaches targeting OTUs.

Main Results:

  • OTUs play critical roles in diverse cellular functions.
  • Dysregulation of OTUs is implicated in various diseases, including cancer.
  • Targeting OTUs presents a promising therapeutic avenue.

Conclusions:

  • OTUs are vital regulators of protein homeostasis with significant pathophysiological roles.
  • Further research into OTU mechanisms can drive the development of novel therapies for human diseases.
  • Targeting OTUs holds potential for treating cancer and other diseases linked to protein homeostasis imbalance.
Keywords:
OTU-deubiquitinasepathophysiological functionprotein stabilitysmall molecule inhibitorstargeted therapyubiquitination

More Related Videos

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay07:05

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

Published on: September 27, 2024

554
Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology10:25

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Published on: November 22, 2024

381

Related Concept Videos

The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.2K
Regulated Protein Degradation02:58

Regulated Protein Degradation

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.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.7K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

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.
These groups modify specific amino acids in a protein....
7.5K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.1K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.9K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.2K