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GSDM family genes meet autophagy

Authors :
Toshihiko Shiroishi
Masaru Tamura
Source :
Biochemical Journal. 469:e5-e7
Publication Year :
2015
Publisher :
Portland Press Ltd., 2015.

Abstract

In the previous issue of Biochemical Journal, Shi et al. [(2015) 468, 325–336] report that Gasdermin (Gsdm) family proteins regulate autophagy activity, which is counter-balanced by the opposite functions of well-conserved N- and C-terminal domains of the proteins. The Gsdm family was originally identified as the causative gene of dominant skin mutations exhibiting alopecia. Each member of the Gsdm gene family shows characteristic expression patterns in the epithelium, which is tissue and differentiation stage-specific. Previous phenotype analyses of mutant mice, biochemical analyses of proteins and genome-wide association studies showed that the Gsdm gene family might be involved in epithelial cell development, apoptosis, inflammation, carcinogenesis and immune-related diseases. To date, however, their molecular function(s) remain unclear. Shi et al. found that mutations in the C-terminal domain of Gsdma3, a member of the Gsdm family, induce autophagy. Further studies revealed that the wild-type N-terminal domain has pro-autophagic activity and that the C-terminal domain conversely inhibits this N-terminal function. These opposite functions of the two domains were also observed in other Gsdm family members. Thus, their study provides a new insight into the function of Gsdm genes in epithelial cell lineage, causality of cancers and immune-related diseases including childhood-onset asthma.

Details

ISSN :
14708728 and 02646021
Volume :
469
Database :
OpenAIRE
Journal :
Biochemical Journal
Accession number :
edsair.doi.dedup.....1c7c37d360650bc2706ad520fda57de4