Nov 10, 2016

USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase

International Journal of Molecular Sciences
Kumi HaradaNobuhiro Nakamura

Abstract

In the endoplasmic reticulum (ER), misfolded and unfolded proteins are eliminated by a process called ER-associated protein degradation (ERAD) in order to maintain cell homeostasis. In the ERAD pathway, several ER-localized E3 ubiquitin ligases target ERAD substrate proteins for ubiquitination and subsequent proteasomal degradation. However, little is known about how the functions of the ERAD ubiquitin ligases are regulated. Recently, USP19, an ER-anchored deubiquitinating enzyme (DUB), has been suggested to be involved in the regulation of ERAD. In this study, HRD1, an ERAD ubiquitin ligase, is shown to be a novel substrate for USP19. We demonstrate that USP19 rescues HRD1 from proteasomal degradation by deubiquitination of K48-linked ubiquitin chains. In addition, the altered expression of USP19 affects the steady-state levels of HRD1. These results suggest that USP19 regulates the stability of HRD1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases.

  • References28
  • Citations5

References

Mentioned in this Paper

Study
USP19 protein, human
HEK293 Cells
Protein Digestion
Regulation of Biological Process
Ubiquitin
COS-7 Cells
T Cell Homeostasis
Endopeptidases
Ubiquitin Activity

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