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Updated: Jun 23, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes
1Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ssun@mdanderson.org
Abstract:
Protein ubiquitination is a reversible reaction, in which the ubiquitin chains are deconjugated by a family of deubiquitinases (DUBs). The presence of a large number of DUBs suggests that they likely possess certain levels of substrate selectivity and functional specificity. Indeed, recent studies show that a tumor suppressor DUB, cylindromatosis (CYLD), has a predominant role in the regulation of NF-kappaB, a transcription factor that promotes cell survival and oncogenesis. NF-kappaB activation involves attachment of K63-linked ubiquitin chains to its upstream signaling factors, which is thought to facilitate protein-protein interactions in the assembly of signaling complexes. By deconjugating these K63-linked ubiquitin chains, CYLD negatively regulates NF-kappaB activation, which may contribute to its tumor suppressor function. CYLD also regulates diverse physiological processes, ranging from immune response and inflammation to cell cycle progression, spermatogenesis, and osteoclastogenesis. Interestingly, CYLD itself is subject to different mechanisms of regulation.
Insights
Cylindromatosis (CYLD) is a deubiquitinase (DUB) that suppresses tumors by inhibiting NF-kappaB signaling. CYLD removes K63-linked ubiquitin chains, preventing cell survival and oncogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein ubiquitination is a reversible post-translational modification crucial for cellular processes.
- Deubiquitinases (DUBs) are enzymes that remove ubiquitin chains, regulating protein function.
- CYLD is a tumor suppressor DUB implicated in regulating NF-kappaB signaling.
Purpose of the Study:
- To elucidate the role of CYLD in regulating NF-kappaB activation.
- To understand the mechanism by which CYLD exerts its tumor suppressor function.
- To explore the broader physiological functions regulated by CYLD.
Main Methods:
- Investigating the deubiquitinase activity of CYLD.
- Analyzing the interaction between CYLD and NF-kappaB signaling pathway components.
- Studying the impact of CYLD on NF-kappaB activation in cellular models.
Main Results:
- CYLD deconjugates K63-linked ubiquitin chains involved in NF-kappaB activation.
- CYLD negatively regulates NF-kappaB signaling, contributing to its tumor suppressor activity.
- CYLD influences diverse processes including immune response, inflammation, and cell cycle.
Conclusions:
- CYLD plays a critical role in negatively regulating NF-kappaB signaling.
- CYLD's function as a tumor suppressor is linked to its control over NF-kappaB.
- CYLD is a key regulator of multiple physiological pathways, highlighting its broad importance.
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