Review
Plant Sciences
Jianjun Zhang, Jiarui Wu, Linchuan Liu, Jianming Li
Summary: Proteins are glycosylated in the ER for proper folding and function, and misfolded proteins can be toxic to cells. Eukaryotic organisms have evolved ERQC mechanisms to monitor and deal with misfolded proteins in order to maintain cellular homeostasis.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jowita Nowakowska-Golacka, Justyna Czapiewska, Hanna Sominka, Natalia Sowa-Rogozinska, Monika Slominska-Wojewodzka
Summary: EDEM1 is an important regulatory factor involved in APP metabolism, as it recognizes misfolded APP proteins and directs them to cytosol for degradation, leading to decreased secretion of Aβ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Ming Yang, Shilu Luo, Xi Wang, Chenrui Li, Jinfei Yang, Xuejing Zhu, Li Xiao, Lin Sun
Summary: The endoplasmic reticulum (ER) is crucial for maintaining cellular homeostasis, and ER-phagy, a selective form of autophagy, helps remove damaged ER to protect cells from harm caused by excessive ER stress. Many receptor-mediated ER-phagy pathways have been discovered in recent years, highlighting the importance of this newly identified autophagy process in maintaining cellular health.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Daria Sicari, Federica G. Centonze, Raphael Pineau, Pierre-Jean Le Reste, Luc Negroni, Sophie Chat, M. Aiman Mohtar, Daniel Thomas, Reynald Gillet, Ted Hupp, Eric Chevet, Aeid Igbaria
Summary: This study identified the accumulation of ER luminal proteins in the cytosol of glioblastoma cells, and demonstrated that ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. The study also showed that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53, suggesting a mechanism named ER to Cytosol Signaling (ERCYS) which provides a selective advantage to tumor cells through gain-of-cytosolic functions.
Review
Biochemistry & Molecular Biology
John C. Christianson, Pedro Carvalho
Summary: This article discusses recent advances in understanding the mechanisms of ERAD and its impact on the regulation of ER functions.
Article
Biochemistry & Molecular Biology
Kohta Miura, Riko Katsuki, Shusei Yoshida, Ren Ohta, Taku Tamura
Summary: ERAD is an essential process for maintaining cell function and preventing ER stress. EDEM1 was found to be involved in accelerating the degradation of EGFR via ERAD, highlighting its physiological role in maintaining specific target proteins and providing a potential approach to regulate the expression of clinically important proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ji An Kang, Young Joo Jeon
Summary: The endoplasmic reticulum (ER) is crucial for protein synthesis and quality control, requiring significant resources to maintain protein homeostasis. Misfolded proteins pose a threat to proteostasis, which can be regulated through ERAD and ER-phagy processes in the ER.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Takashi Kikuma, Haruka Ibuki, Masaya Nakamoto, Akira Seko, Yukishige Ito, Yoichi Takeda
Summary: It has been discovered that EDEM3 plays a significant role in the protein quality control in the endoplasmic reticulum (ER), by converting specific glycans into other types of glycans. Additionally, the activity of EDEM3 is enhanced through interaction with ERp46. This study provides new insights into the enzymatic properties of EDEM3 and the use of artificial glycan substrates to study ERAD mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Nuno Maia, Sven Potelle, Hamide Yildirim, Sandrine Duvet, Shyam K. Akula, Celine Schulz, Elsa Wiame, Alexander Gheldof, Katherine O'Kane, Abbe Lai, Karen Sermon, Maia Proisy, Philippe Loget, Tania Attie-Bitach, Chloe Quelin, Ana Maria Fortuna, Ana Rita Soares, Arjan P. M. de Brouwer, Emile Van Schaftingen, Marie-Cecile Nassogne, Christopher A. Walsh, Katrien Stouffs, Paula Jorge, Anna C. Jansen, Francois Foulquier
Summary: This study reports on six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1 gene from four different families. These individuals exhibit dysmorphic features, congenital anomalies, and brain abnormalities. The pathogenicity of MAN2C1 variants is confirmed, and it is demonstrated that these variants lead to accumulation and delay in the processing of fOSs in cells.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Mari A. Piirainen, Alexander D. Frey
Summary: Yeasts are widely used for biopharmaceutical production, but N-glycosylated biopharmaceuticals manufactured with yeasts are missing on the market. N-linked glycans play crucial roles in protein properties and folding, but current glycoengineering approaches face challenges.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Immunology
Stephanie Trezise, Isabella Y. Kong, Edwin D. Hawkins, Marco J. Herold, Simon N. Willis, Stephen L. Nutt
Summary: In this study, CRISPR/Cas9 technology was used to screen for regulators of terminal differentiation and antibody production in primary B cells. Positive regulators (Sec61a1, Hspa5) and negative regulators (Arhgef18, Pold1, Pax5, Ets1) of differentiation were identified. Genes that limited the proliferative capacity of activated B cells (Sumo2, Vcp, Selk) were also discovered. Furthermore, 35 genes required for antibody secretion were identified, including those involved in endoplasmic reticulum-associated degradation, the unfolded protein response, and post-translational protein modifications. These findings have implications for drug targets in antibody-mediated diseases and potential gene candidates for primary immune deficiency.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Ting Cao, Binfeng Peng, Xiangping Zhou, Jialun Cai, Yun Tang, Jie Luo, Haitao Xie, Ji Zhang, Shuangquan Liu
Summary: The endoplasmic reticulum (ER) is a crucial multifunctional organelle responsible for correct folding and assembly of secretory and transmembrane proteins. Perturbations in ER function can lead to ER stress, activating the unfolded protein response (UPR) to cope with misfolded protein accumulation. If the imbalance cannot be restored, it may lead to cell death or diseases. The UPR is a coordination system that regulates transcription and translation to help cells recover ER homeostasis. The integrated signaling system in cells includes ER-associated degradation (ERAD), autophagy, hypoxia signaling, and mitochondrial biogenesis to cope with ER stress.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Plant Sciences
Sofia Reyes-Impellizzeri, Adrian A. Moreno
Summary: This review focuses on the impact of alterations in components of ERQC, ERAD, and UPR on plant responses to abiotic stresses. Evidence shows a clear connection between ERAD and UPR mechanisms, but the connection of ERQC components with these processes or their possible client proteins is lacking. Proteomics approaches are suggested to uncover the identity of these proteins and their connection to ER proteostasis.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Nicola A. Scott, Laura J. Sharpe, Andrew J. Brown
Summary: MARCHF6 is a large multi-pass E3 ubiquitin ligase embedded in the membranes of the endoplasmic reticulum, participating in endoplasmic reticulum associated degradation and being regulated by cholesterol. It plays a role in cell metabolism and its regulation, substrates, and role in human health and disease are still not fully understood.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Review
Biochemistry & Molecular Biology
Keisuke Mochida, Hitoshi Nakatogawa
Summary: Autophagy is a degradation system in eukaryotic cells that controls the mass and functions of organelles by degrading excess or defective portions. The endoplasmic reticulum (ER) is an organelle with specific functions that dynamically changes its mass and shape to maintain or regulate its functions. Elaborate mechanisms are required for the proper degradation of the ER.