A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin

@article{Omura2006AUL,
  title={A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin},
  author={Tomohiro Omura and Masayuki Kaneko and Yasunobu Okuma and Yasuko Orba and Kazuo Nagashima and Ryosuke Takahashi and Noboru Fujitani and Satoshi Matsumura and Akihisa Hata and Kyoko Kubota and Karin Murahashi and Takashi Uehara and Yasuyuki Nomura},
  journal={Journal of Neurochemistry},
  year={2006},
  volume={99}
}
It has been proposed that in autosomal recessive juvenile parkinsonism (AR‐JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum‐associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin‐associated endothelin receptor‐like receptor (Pael‐R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress… 
Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain
TLDR
It is demonstrated that HRD1 immunoreactivity was expressed widely in the substantia nigra pars compacta containing dopaminergic neurons and was expressed in the cerebral cortex, hippocampus, dentate gyrus, striatum, globus pallidus, and Purkinje cells of the cerebellar cortex, suggesting that HRd1 may play an important role in maintaining higher brain function, including motor function or learning and memory.
Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains.
TLDR
It is shown that the proline-rich domain of HRD1 is necessary to promote the degradation of Pael-R and that the protein's transmembrane domain is needed to transfer Pae-R from the endoplasmic reticulum (ER) to the cytosol.
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  • M. Kaneko
  • Chemistry, Medicine
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
  • 2016
TLDR
HRD1 protein was insolubilized by oxidative stress, resulting in the accumulation of HRD1 into the aggresome, which might be involved in a vicious cycle of increased Aβ production and Aβ-induced oxidative stress in Alzheimer's disease pathogenesis.
Ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) prevents cell death in a cellular model of Parkinson's disease.
TLDR
It is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD.
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TLDR
The results suggest that the breakdown of HRD1-mediated ERAD causes Aβ generation and ER stress, possibly linked to AD.
Deletion of Herp facilitates degradation of cytosolic proteins
TLDR
Deletion of Herp enhanced the amount of ubiquitinated protein in the cytosol during proteasomal inhibition, although it did not affect the activity or expression of proteasome, suggesting that ERAD molecule Herp may delay the degradation of cytosolic proteins at the ubiquitination step.
Effects of Oxidative Stress on the Solubility of HRD1, a Ubiquitin Ligase Implicated in Alzheimer’s Disease
TLDR
It is shown that HRD1 protein was insolubilized by oxidative stress but not by other Alzheimer’s disease-related molecules and stressors, such as amyloid β, tau, and endoplasmic reticulum stress.
Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum.
TLDR
It is reported that Hrd1, also known as synoviolin, targets gp78 for proteasomal degradation independent of the ubiquitin ligase activity of gp78, without evidence of a reciprocal effect.
Endoplasmic Reticulum Stress and Parkinson's Disease: The Role of HRD1 in Averting Apoptosis in Neurodegenerative Disease
TLDR
Recent progress in the studies on the mechanism of ER stress-induced neuronal death related to PD are reviewed, particularly focusing on the involvement of HRD1 in the prevention of neuronal death as well as a potential therapeutic approach for PD based on the upregulation ofHRD1.
Parkin reverses intracellular β‐amyloid accumulation and its negative effects on proteasome function
TLDR
Parkin is cytoprotective, partially by increasing the removal of cellular Aβ through a proteasome‐dependent pathway.
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TLDR
It is demonstrated that Parkin is an E3 enzyme and suggested that it is involved in the ubiquitination pathway for misfolded proteins derived from endoplasmic reticulum and contributes to protection from neurotoxicity induced by unfolded protein stresses.
Human HRD1 protects against ER stress‐induced apoptosis through ER‐associated degradation1
TLDR
The identification and characterization of a human homolog to yeast Hrd1p is reported, which suggests that the production of HRD1 is up‐regulated to protect against ER stress‐induced apoptosis by degrading unfolded proteins accumulated in the ER.
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TLDR
The structure and function of the putative human orthologue of yeast Hrd1p/Der3p, designated human HRD1, is characterized, showing that humanHRD1 is a non-glycosylated, stable ER protein with a cytosolic RING-H2 finger domain, suggesting that human HRd1 is an E3 ubiquitin ligase involved in protein degradation.
An Unfolded Putative Transmembrane Polypeptide, which Can Lead to Endoplasmic Reticulum Stress, Is a Substrate of Parkin
TLDR
It is shown that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP.
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TLDR
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TLDR
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TLDR
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TLDR
The retro-translocon seems to be build up at least by the Sec61 pore, Der3p/Hrd1p and Hrd3p and mediates both retrograde transport and ubiquitination of substrates of the endoplasmic reticulum degradation machinery.
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TLDR
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TLDR
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