The deafness gene GSDME: its involvement in cell apoptosis, secondary necrosis, and cancers
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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.
KeywordsGSDME DFNA5 Secondary necrosis Apoptosis Hearing loss Cancer
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.
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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Conflict of interest
The authors declare that they have no conflict of interest.
- Akino K, Toyota M, Suzuki H, Imai T, Maruyama R, Kusano M, Nishikawa N, Watanabe Y, Sasaki Y, Abe T, Yamamoto E, Tarasawa I, Sonoda T, Mori M, Imai K, Shinomura Y, Tokino T (2007) Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer. Cancer Sci 98(1):88–95CrossRefGoogle Scholar
- Cheng J, Han DY, Dai P, Sun HJ, Tao R, Sun Q, Yan D, Qin W, Wang HY, Ouyang XM, Yang SZ, Cao JY, Feng GY, Du LL, Zhang YZ, Zhai SQ, Yang WY, Liu XZ, He L, Yuan HJ (2007) A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late-onset non-syndromic hearing loss in a Chinese family. Clin Genet 72(5):471–477CrossRefGoogle Scholar
- Fujikane T, Nishikawa N, Toyota M, Suzuki H, Nojima M, Maruyama R, Ashida M, Ohe-Toyota M, Kai M, Nishidate T, Sasaki Y, Ohmura T, Hirata K, Tokino T (2010) Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer. Breast Cancer Res Treat 122(3):699–710CrossRefGoogle Scholar
- Masuda Y, Futamura M, Kamino H, Nakamura Y, Kitamura N, Ohnishi S, Miyamoto Y, Ichikawa H, Ohta T, Ohki M, Kiyono T, Egami H, Baba H, Arakawa H (2006) The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage. J Hum Genet 51(8):652–664CrossRefGoogle Scholar
- Van Rossom S, Op de Beeck K, Franssens V, Swinnen E, Schepers A, Ghillebert R, Caldara M, Van Camp G, Winderickx J (2012) The splicing mutant of the human tumor suppressor protein DFNA5 induces programmed cell death when expressed in the yeast Saccharomyces cerevisiae. Front Oncol 2:77Google Scholar
- Van Rossom S, Op de Beeck K, Hristovska V, Winderickx J, Van Camp G (2015) The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways. Front Cell Neurosci 9:231Google Scholar