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

Naunyn Schmiedebergs Arch Pharmacol. 2019 Sep;392(9):1043-1048. doi: 10.1007/s00210-019-01674-7. Epub 2019 Jun 22.

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.

Keywords: Apoptosis; Cancer; DFNA5; GSDME; Hearing loss; Secondary necrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Deafness / genetics*
  • Humans
  • Necrosis
  • Neoplasms / genetics*
  • Receptors, Estrogen / genetics*

Substances

  • GSDME protein, human
  • Receptors, Estrogen