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Review
. 2015;16(4):284-94.
doi: 10.2174/1389450115666141024152421.

CYLD-mediated signaling and diseases

Bryan J Mathis, Yimu Lai, Chen Qu, Joseph S Janicki, Taixing Cui  1
Affiliations
Review

CYLD-mediated signaling and diseases

Bryan J Mathis et al. Curr Drug Targets. 2015.

Abstract

The conserved cylindromatosis (CYLD) codes for a deubiquitinating enzyme and is a crucial regulator of diverse cellular processes such as immune responses, inflammation, death, and proliferation. It directly regulates multiple key signaling cascades, such as the Nuclear Factor kappa B [NFkB] and the Mitogen-Activated Protein Kinase (MAPK) pathways, by its catalytic activity on polyubiquitinated key intermediates. Several lines of emerging evidence have linked CYLD to the pathogenesis of various maladies, including cancer, poor infection control, lung fibrosis, neural development, and now cardiovascular dysfunction. While CYLD-mediated signaling is cell type and stimuli specific, the activity of CYLD is tightly controlled by phosphorylation and other regulators such as Snail. This review explores a broad selection of current and past literature regarding CYLD's expression, function and regulation with emerging reports on its role in cardiovascular disease.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

Figures

Fig. 1
Fig. 1
The canonical TNFR to Nf-kB pathway.
Fig. 2
Fig. 2
Fig. (2A) The regulation of CYLD is complex and multimodal. As the key effector of K63-linked deubiquitination, which transduces cellular signals, CYLD is tightly regulated at the transcript and protein level, as well as by phosphorylation. Fig. (2B). CYLD’s regulation of the immune system. Fig. (2C). CYLD’s interaction with important regulators of necrosis and development.
Fig. 2
Fig. 2
Fig. (2A) The regulation of CYLD is complex and multimodal. As the key effector of K63-linked deubiquitination, which transduces cellular signals, CYLD is tightly regulated at the transcript and protein level, as well as by phosphorylation. Fig. (2B). CYLD’s regulation of the immune system. Fig. (2C). CYLD’s interaction with important regulators of necrosis and development.
Fig. 2
Fig. 2
Fig. (2A) The regulation of CYLD is complex and multimodal. As the key effector of K63-linked deubiquitination, which transduces cellular signals, CYLD is tightly regulated at the transcript and protein level, as well as by phosphorylation. Fig. (2B). CYLD’s regulation of the immune system. Fig. (2C). CYLD’s interaction with important regulators of necrosis and development.
Fig. 3
Fig. 3
CYLD’s regulation of factors known to play an important role in cardiovascular disease.
Fig. 4
Fig. 4
CYLD in cardiovascular disease model. CYLD may affect any or all of these pathways to regulate the formation of vascular lesions.
See this image and copyright information in PMC

References

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