タンパク質寿命が制御するシン・バイオロジー

Endoplasmic reticulum-associated degradation (ERAD) is a crucial intracellular quality control system by the ubiquitin-proteasome system. Deletion of key components of ERAD results in embryonic lethality in mice, underscoring the physiological significance of ERAD in development. Although the ERAD-related molecules responsible for the execution of ERAD have been elucidated in considerable detail, most analyses of this mechanism have been performed using model proteins with pathogenic mutations. It is unclear how many endogenous proteins without mutations are degraded by the ERAD pathway. Not only misfolded proteins, but also constitutively substrates degraded by the ERAD have been reported, and this pathway is now understood as a system that actively regulates the proteome.
In this study, we comprehensively identify ubiquitinated glycoproteins from mouse embryos in which proteasome activity is attenuated by deletion of NGLY1, thereby providing a proteome-wide understanding of ERAD, which is important in development. We aim to understand intrinsic signal of substrates for ERAD by analyzing the correspondence between identified substrates and ERAD targeting molecules.

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