scholarly journals Lys11- and Lys48-linked ubiquitin chains interact with p97 during endoplasmic-reticulum-associated degradation

2014 ◽  
Vol 459 (1) ◽  
pp. 205-216 ◽  
Author(s):  
Matthew Locke ◽  
Julia I. Toth ◽  
Matthew D. Petroski
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Endoplasmic Reticulum Membrane ◽  
Endoplasmic Reticulum Associated Degradation

This study provides evidence that p97 interacts with proteins modified with Lys11- and Lys48-linked ubiquitin chains at the endoplasmic reticulum membrane, suggesting roles for these signals in protein quality control.

scholarly journals Endoplasmic reticulum associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity

2019 ◽  
Author(s):  
Lu Liu ◽  
Ayaka Inoki ◽  
Kelly Fan ◽  
Fengbiao Mao ◽  
Guojun Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Stem Cell ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Mtor Activity

SummaryMany tissue-specific stem cells require quiescence to sustain stem cell pool and maintain lifelong tissue integrity. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis and metabolic activities are significantly reduced. Here, we report that endoplasmic reticulum associated degradation (ERAD) is required to preserve the function of quiescent hematopoietic stem cells (HSC). The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyper-proliferation which leads to reduced self-renewal and HSC depletion. ERAD deficiency induces a non-apoptotic ER stress and activates unfolded protein response (UPR). Furthermore, Sel1L knockout leads to mTOR activation, and mTOR inhibition rescues the HSC defects in Sel1L knockout mice. Protein quality control is, therefore, tightly regulated and actively engaged in quiescent HSCs. Sel1L/Hrd1 ERAD maintains HSC quiescence and self-renewal via restricting mTOR activity.

scholarly journals Endoplasmic Reticulum-Mediated Protein Quality Control and Endoplasmic Reticulum-Associated Degradation Pathway Explain the Reduction of N-glycoprotein Level Under the Lead Stress

2021 ◽  
Vol 11 ◽  
Author(s):  
Hong Du ◽  
Canqi Zheng ◽  
Muhmmad Aslam ◽  
Xihui Xie ◽  
Wanna Wang ◽  
...  
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Level ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Misfolded Proteins ◽  
Pb Stress ◽  
Endoplasmic Reticulum Associated Degradation ◽  
High Lead ◽  
Erad Pathway

Different anthropogenic activities result in the continuous increase of metal lead (Pb) in the environment and adversely affect living organisms. Therefore, it is important to investigate the tolerance mechanism in a model organism. Chlamydomonas reinhardtii is an important green eukaryotic model microalga for studying different kinds of biological questions. In this study, the responses of C. reinhardtii were revealed via a comprehensive approach, including physiological, genomic, transcriptomic, glycomic, and bioinformatic techniques. Physiological results showed that the growth rate and soluble protein content were significantly reduced under the high lead stress. Also, the results obtained from the genomic and transcriptomic analyses presented that the endoplasmic reticulum-mediated protein quality control (ERQC) system and endoplasmic reticulum-associated degradation (ERAD) pathway were activated under the third day of high lead stress. The unique upregulated protein disulfide isomerase genes on the ERQC system were proposed to be important for the protein level and protein quality control. The accumulation of specific N-glycans indicated that specific N-glycosylation of proteins might alter the biological functions of proteins to alleviate the Pb stress in alga and/or lead to the degradation of incomplete/misfolded proteins. At the same time, it was observed that genes involved in each process of ERAD were upregulated, suggesting that the ERAD pathway was activated to assist the degradation of incomplete/misfolded proteins. Therefore, it is reasonable to speculate that the reduction of protein level under the high lead stress was related to the activated ERQC system and QRAD pathway. Our findings will provide a solid and reliable foundation and a proposed ERAD working model for further in-depth study of the ERQC system and ERAD pathway under the Pb stress and even other biotic and abiotic stresses.

scholarly journals Characterization of an ERAD Gene as VPS30/ATG6 Reveals Two Alternative and Functionally Distinct Protein Quality Control Pathways: One for Soluble Z Variant of Human α-1 Proteinase Inhibitor (A1PiZ) and Another for Aggregates of A1PiZ

2006 ◽  
Vol 17 (1) ◽  
pp. 203-212 ◽  
Author(s):  
Kristina B. Kruse ◽  
Jeffrey L. Brodsky ◽  
Ardythe A. McCracken
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Proteinase Inhibitor ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Carboxypeptidase Y ◽  
Complex Nature ◽  
Secretion Pathway ◽  
Golgi Network ◽  
Yeast Mutants

The Z variant of human α-1 proteinase inhibitor (A1PiZ) is a substrate for endoplasmic reticulum-associated protein degradation (ERAD). To identify genes required for the degradation of this protein, A1PiZ degradation-deficient (add) yeast mutants were isolated. The defect in one of these mutants, add3, was complemented by VPS30/ATG6, a gene that encodes a component of two phosphatidylinositol 3-kinase (PtdIns 3-kinase) complexes: complex I is required for autophagy, whereas complex II is required for the carboxypeptidase Y (CPY)-to-vacuole pathway. We found that upon overexpression of A1PiZ, both PtdIns 3-kinase complexes were required for delivery of the excess A1PiZ to the vacuole. When the CPY-to-vacuole pathway was compromised, A1PiZ was secreted; however, disruption of autophagy led to an increase in aggregated A1PiZ rather than secretion. These results suggest that excess soluble A1PiZ transits the secretion pathway to the trans-Golgi network and is selectively targeted to the vacuole via the CPY-to-vacuole sorting pathway, but excess A1PiZ that forms aggregates in the endoplasmic reticulum is targeted to the vacuole via autophagy. These findings illustrate the complex nature of protein quality control in the secretion pathway and reveal multiple sites that recognize and sort both soluble and aggregated forms of aberrant or misfolded proteins.

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