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The deafness gene GSDME: its involvement in cell apoptosis, secondary necrosis, and cancers

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Abstract

Gasdermin E (GSDME), also called DFNA5, is a member of the gasdermin family. GSDME is involved in the regulation of apoptosis and necrosis. The N-terminal domain of GSDME displays an apoptosis-inducing activity while the C-terminal domain may serve as an apoptosis-inhibiting regulator by shielding the N-terminal domain. Besides its function in the regulation of apoptosis, GSDME was recently reported to be a substrate of caspase-3 and cleavage of GSDME by caspase-3 into necrotic N-terminal fragment leads to the induction of secondary necrosis. GSDME was first identified as a deafness gene because its mutation was associated with a specific form of autosomal dominant progressive sensorineural hearing loss. Furthermore, GSDME has been considered a tumor suppressor implicated in several types of cancer. This mini-review summarized recent reports relevant to the functions of GSDME in the regulation of apoptosis and necrosis as well as its clinical relevance.

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Funding

This work was supported by the National Natural Science Foundation of China, China (No. 81573430 to Xiu-Ju Luo; No. 81872873 to Jun Peng) and Natural Science Foundation of Hunan Province, China (No. 2015JJ2156 to Xiu-Ju Luo).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, 410013, China

    Yue-Qi Li & Xiu-Ju Luo

  2. Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Jing-Jie Peng

  3. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China

    Jun Peng

  4. Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China

    Jun Peng

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  1. Yue-Qi Li
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YQ Li and JJ Peng drafted the manuscript, and J Peng and XJ Luo revised the manuscript. All authors agreed the final version of the manuscript and approved the submission.

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Correspondence to Xiu-Ju Luo.

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Li, YQ., Peng, JJ., Peng, J. et al. The deafness gene GSDME: its involvement in cell apoptosis, secondary necrosis, and cancers. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1043–1048 (2019). https://doi.org/10.1007/s00210-019-01674-7

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  • DOI: https://doi.org/10.1007/s00210-019-01674-7

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