Article
Oncology
Mary E. Law, Elham Yaaghubi, Amanda F. Ghilardi, Bradley J. Davis, Renan B. Ferreira, Jin Koh, Sixue Chen, Sadie F. DePeter, Christopher M. Schilson, Chi-Wu Chiang, Coy D. Heldermon, Peter Norgaard, Ronald K. Castellano, Brian K. Law
Summary: Breast cancer mortality remains high, and there is a need for safer and more effective treatments. Disulfide bond Disrupting Agents (DDAs) have been identified as a potential class of anticancer compounds that specifically target EGFR and HER2 overexpressing cancer cells. The study found that DDAs act by downregulating EGFR, HER2, and HER3 and activating Death Receptors 4 and 5 (DR4/5). Further analysis revealed that AGR2, PDIA1, and ERp44 are the target proteins of DDAs. DDAs disrupt the mixed disulfide bonds between PDIA1, ERp44, and their client proteins, and enhance basal DR5 oligomerization by targeting AGR2 and ERp44.
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
Yoshiyuki Matsuo
Summary: The presence of a large number of thioredoxin superfamily members indicates a complex redox-based regulation mechanism in mammalian cells. Thioredoxin-like proteins are found in the endoplasmic reticulum, with a specific family of TMX proteins residing in the ER membrane and playing crucial roles in cellular processes. Further research is needed to understand the physiological roles of TMX family proteins and how they can be targeted for drug discovery in various human diseases.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Cintia E. Citterio, Kookjoo Kim, Bhavana Rajesh, Kevin Pena, Oliver Biggs Clarke, Peter Arvan
Summary: The study found that defects in the trafficking of thyroglobulin can lead to hypothyroidism. By conducting mutation experiments, it was discovered that different mutants have distinct effects on the quality control of thyroglobulin, inhibiting domain-specific folding, folding via regional contact, neither, or both.
Article
Biochemistry & Molecular Biology
Leena Haataja, Anoop Arunagiri, Anis Hassan, Kaitlin Regan, Billy Tsai, Balamurugan Dhayalan, Michael A. Weiss, Ming Liu, Peter Arvan
Summary: Efficient export of proinsulin from the endoplasmic reticulum requires the formation of specific disulfide bonds, while disrupting certain pairings may improve trafficking in some mutants. Mutations causing Mutant INS gene-induced Diabetes of Youth (MIDY) often result in perturbed proinsulin disulfide bond formation, with potential for allele-specific pharmacological targeting in the future.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biology
Motonori Matsusaki, Rina Okada, Yuya Tanikawa, Shingo Kanemura, Dai Ito, Yuxi Lin, Mai Watabe, Hiroshi Yamaguchi, Tomohide Saio, Young-Ho Lee, Kenji Inaba, Masaki Okumura
Summary: The physiological functions of proteins are determined by their unique three-dimensional structures, with conserved disulfide-catalysts and chaperone networks playing a crucial role in correct protein folding and prevention of aggregation. Disruption of these networks is implicated in pathology. Complex formation among PDIs accelerates protein folding and prevents aggregation.
Article
Multidisciplinary Sciences
Guochen Qin, Menghuan Qu, Bei Jia, Wei Wang, Zhuojun Luo, Chun-Peng Song, W. Andy Tao, Pengcheng Wang
Summary: This study developed a highly sensitive method for detecting S-nitrosylation peptides, allowing for quantitative identification of S-nitrosylated proteins and revealing a key role of GSNOR1 in regulating endoplasmic reticulum functions in Arabidopsis.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Philip John Robinson, Marie Anne Pringle, Bethany Fleming, Neil John Bulleid
Summary: Proteins in the secretory pathway require correct disulfide pairings for proper folding. Two important members of the protein disulfide isomerase (PDI) family, ERp57 and ERdj5, have unclear roles in disulfide formation, but ERp57 is involved in the isomerisation of non-native disulfides in glycoproteins. Alternative PDIs can compensate for the absence of ERp57 in isomerising glycoprotein disulfides, but only when a robust reductive pathway is present. ERdj5 is required for this alternative pathway as a reductase. These findings clarify the essential functions of two PDIs in the cell and highlight the distinctions between formation, reduction, and isomerisation of disulfide bonds.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Yuki Oku, Masahiro Kariya, Takaaki Fujimura, Jun Hoseki, Yasuyoshi Sakai
Summary: Proteasome inhibition initially leads to oxidation of the ER, which gradually recovers to a reductive state. This is accompanied by an increase in both oxidized and reduced glutathione in the microsomal fraction, while total intracellular glutathione decreases. The reduction of the ER is suppressed by pretreatment of a glutathione synthesis inhibitor or by knockdown of ATF4, indicating a cellular adaptation of ER redox homeostasis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Filippo Fornasiero, Cristina Scapin, Maurizio Vitadello, Paola Pizzo, Luisa Gorza
Summary: This study reveals the role of Grp94/gp96 in cytoprotection by regulating SERCA2 and improving Ca2+ homeostasis. It demonstrates that Grp94 can co-immunoprecipitate with non-client proteins and form a multiprotein complex involving active nNOS, contributing to antioxidant cytoprotection. Moreover, in breast cancer cells, the presence of Grp94-nNOS, SERCA2, and PMCA co-immunoprecipitation is associated with increased oxidant-induced apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Fisheries
Yu Wang, Hongjing Zhao, Menghao Guo, Mengyao Mu, Hui Zong, Mingwei Xing
Summary: Arsenic contamination in water bodies has adverse effects on aquatic organisms, while zinc plays a crucial role in cellular balance and biological functions. The interaction between arsenic and zinc in common carp has been less studied. Arsenic alters intestinal morphology and tight junction proteins, leading to physiological and cellular abnormalities, including oxidative stress, inflammation, detoxification, and immune suppression. Zinc supplementation can mitigate these damages by activating the antioxidant system, serving as an effective treatment and prevention for arsenic poisoning.
Article
Biochemistry & Molecular Biology
Qiu-Ying Du, Fu-Chun Huo, Wen-Qi Du, Xiao-Lin Sun, Xin Jiang, Lan-Sheng Zhang, Dong-Sheng Pei
Summary: N6-methyladenosine (m6A), the most abundant chemical modification on mRNA, plays important roles in various biological processes. This study reveals that METTL3, a core member of the m6A methyltransferase family, is upregulated in cervical cancer (CC) and serves as an independent prognostic factor. Mechanistically, the transcription factor ETS1 recruits P300 and WDR5 to mediate histone modification in the promoter region of METTL3, leading to its transcription activation. Additionally, METTL3-mediated m6A modification regulates the expression of TXNDC5, promoting proliferation and metastasis of CC cells.
Article
Pharmacology & Pharmacy
Shen-Jun Yuan, Chao Wang, Hua-Zhen Xu, Yan Liu, Mei-Yan Zheng, Ke Li, Shi-Kuan Sun, Naoki Komatsu, Li Zhao, Xiao Chen
Summary: This study revealed that Nano-DOX, conjugated with polyglycerol-coated nanodiamonds, exhibited distinct intracellular distribution compared to free DOX. Nano-DOX induced less endoplasmic reticulum stress and DNA damage, as well as weaker pro-inflammatory signaling pathway activation, when compared to free DOX. These findings suggest that chemotherapy in nano form can have altered cellular effects of the drug.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Oncology
Yuan Zhang, Lei Liu, Minghui Zhou, Yujie Zhang, Hongxia Su, Dong Dong, Jia Wang
Summary: This study revealed that PPIB regulates cell proliferation in HeLa cells through alternative splicing, primarily enriched in signaling pathways related to inflammation and immune response.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2022)
Article
Integrative & Complementary Medicine
Hyun Ju Kim, Mijeong Kim
Summary: The study aimed to determine the role of diallyl disulfide (DADS) in attenuating ER stress. The results showed that DADS can suppress diet-induced hypercholesterolemia by regulating ER stress markers and may be a good candidate for treating individuals with high cholesterol.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2023)
