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.
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July 2015
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July 06 2015
GSDM family genes meet autophagy
Masaru Tamura;
Masaru Tamura
*Technology and Development Team for Mouse Phenotype Analysis, Bio-Resource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
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Toshihiko Shiroishi
Toshihiko Shiroishi
1
†Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 14 2015
Accepted:
May 18 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 469 (2): e5–e7.
Article history
Received:
May 14 2015
Accepted:
May 18 2015
Connected Content
This is a commentary on:
Loss of conserved Gsdma3 self-regulation causes autophagy and cell death
Citation
Masaru Tamura, Toshihiko Shiroishi; GSDM family genes meet autophagy. Biochem J 15 July 2015; 469 (2): e5–e7. doi: https://doi.org/10.1042/BJ20150558
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