• Corpus ID: 33922397

A ubiquitin ligase HRD 1 promotes the degradation of Pael receptor , a substrate of

  title={A ubiquitin ligase HRD 1 promotes the degradation of Pael receptor , a substrate of},
  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},
It has been proposed that in autosomal recessive juvenile parkinsonism (AR-JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum (ER)-associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, leads to ER stress, causing neuronal death. We previously reported that human E3 HRD1 in the ER protects against ER stress-induced apoptosis. This study shows that (1) HRD1… 


Parkin Suppresses Unfolded Protein Stress-induced Cell Death through Its E3 Ubiquitin-protein Ligase Activity*
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
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.
Human HRD1 Is an E3 Ubiquitin Ligase Involved in Degradation of Proteins from the Endoplasmic Reticulum*
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
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.
In Vivo Action of the HRD Ubiquitin Ligase Complex: Mechanisms of Endoplasmic Reticulum Quality Control and Sterol Regulation
It appears that the physiologically regulated, HRD-dependent degradation of HMGR is effected by a programmed structural transition from a stable protein to a quality control substrate.
A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1.
Immunofluorescence imaging confirms that the endogenous hHrd1 resides in the ER and in vitro assay demonstrates that it has a ubiquitin-ligase activity, but the homology between the human and yeast Hrd1 is limited to the N-terminal domain of the proteins, and hHRD1 does not appear to be involved in the degradation of mammalian HMGR.
Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
In epithelial cells, tyrosine kinases induce the tyrosine phosphorylation and ubiquitination of the E-cadherin complex, which induces endocytosis of E-cadherin. With a modified yeast 2-hybrid system,
Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila
This study shows in an organismal system that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic neurons and suggests that manipulating Parkin expression may provide a novel avenue of PD therapy.
Cbl-b, a RING-type E3 Ubiquitin Ligase, Targets Phosphatidylinositol 3-Kinase for Ubiquitination in T Cells*
It is shown that Cbl-b interacts with and induces ubiquitin conjugation to the p85 regulatory subunit of phosphatidylinositol 3-kinase, an upstream regulator of Vav, a guanine nucleotide exchange factor that is implicated in setting the threshold of T lymphocyte activation.
A regulatory link between ER-associated protein degradation and the unfolded-protein response.
It is shown that Ubc1 acts as a further ubiquitin-conjugating enzyme in this pathway, demonstrating, for the first time, a regulatory loop between ERAD and the UPR, which is essential for normal growth of yeast cells.