FEBS Open Bio (Aug 2023)

Selective proteasome degradation of C‐terminally‐truncated human WFS1 in pancreatic beta cells

  • Hiraku Tokuma,
  • Daisuke Sakano,
  • Katsuya Tanabe,
  • Yukio Tanizawa,
  • Nobuaki Shiraki,
  • Shoen Kume

DOI
https://doi.org/10.1002/2211-5463.13674
Journal volume & issue
Vol. 13, no. 8
pp. 1405 – 1414

Abstract

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Wolfram syndrome is a monogenic disease mainly caused by mutations in the WFS1 gene. Mutations in the WFS1 gene give rise to diabetes. Here, we characterized mutant WFS1 proteins by studying the stability of full‐length wild‐type (WT) WFS1, a missense mutant P724L, and two C‐terminally truncated mutants, W837X and Y652X. We compared their stability by overexpressing them in MIN6 and HEK293T cells. The C‐terminally truncated mutants W837X and Y652X are degraded more rapidly than the missense P724L mutant or wild‐type WFS1 in MIN6 cells. In contrast, Y652X is more stable than WT or other mutant WFS1 proteins in HEK293T. In conclusion, we found that C‐terminally truncated WFS1 mutants are selectively degraded in a cell type‐specific manner.

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