keyword
https://read.qxmd.com/read/38201525/expression-of-3q-oncogene-sec62-predicts-survival-in-head-and-neck-squamous-cell-carcinoma-patients-treated-with-primary-chemoradiation
#1
JOURNAL ARTICLE
Maximilian Linxweiler, Matthias Schneider, Sandrina Körner, Moritz Knebel, Lukas Alexander Brust, Felix Leon Braun, Silke Wemmert, Mathias Wagner, Markus Hecht, Bernhard Schick, Jan Philipp Kühn
Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome...
December 24, 2023: Cancers
https://read.qxmd.com/read/38153175/control-of-nuclear-envelope-dynamics-during-acute-er-stress-by-linc-complexes-disassembly-and-selective-asymmetric-autophagy-of-the-outer-nuclear-membrane
#2
JOURNAL ARTICLE
Marika K Kucińska, Maurizio Molinari
The endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increase or reduce ER size and activities, respectively. If dynamic changes of the ER are transmitted to the contiguous NE was not known. In our recent publication, we report on the transmission of stress-induced ER expansion to the NE, which requires disassembly of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes deputed to ensure a physical connection between the cytoplasmic cytoskeleton and the nuclear lamina and to maintain the width between INM and ONM within 50 nm...
December 28, 2023: Autophagy
https://read.qxmd.com/read/38021175/methionine-restriction-impairs-degradation-of-a-protein-that-aberrantly-engages-the-endoplasmic-reticulum-translocon
#3
JOURNAL ARTICLE
Avery M Runnebohm, Christopher J Indovina, Samantha M Turk, Connor G Bailey, Cade J Orchard, Lauren Wade, Danielle L Overton, Brian J Snow, Eric M Rubenstein
Proteins that persistently engage endoplasmic reticulum (ER) translocons are degraded by multiple translocon quality control (TQC) mechanisms. In Saccharomyces cerevisiae , the model translocon-associated protein Deg1 -Sec62 is subject to ER-associated degradation (ERAD) by the Hrd1 ubiquitin ligase and, to a lesser extent, proteolysis mediated by the Ste24 protease. In a recent screen, we identified nine methionine-biosynthetic genes as candidate TQC regulators. Here, we found methionine restriction impairs Hrd1-independent Deg1 -Sec62 degradation...
2023: microPublication. Biology
https://read.qxmd.com/read/37787092/dual-sec62-ki67-immunocytochemistry-of-liquid-based-cytological-preparations-represents-a-highly-valid-biomarker-for-non-invasive-detection-of-head-and-neck-squamous-cell-carcinomas
#4
JOURNAL ARTICLE
Jan Philipp Kühn, Stefanie Speicher, Barbara Linxweiler, Sandrina Körner, Hugo Rimbach, Mathias Wagner, Erich Franz Solomayer, Bernhard Schick, Maximilian Linxweiler
BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid-based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non-invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions...
October 3, 2023: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://read.qxmd.com/read/37762469/quantitative-mass-spectrometry-characterizes-client-spectra-of-components-for-targeting-of-membrane-proteins-to-and-their-insertion-into-the-membrane-of-the-human-er
#5
REVIEW
Martin Jung, Richard Zimmermann
To elucidate the redundancy in the components for the targeting of membrane proteins to the endoplasmic reticulum (ER) and/or their insertion into the ER membrane under physiological conditions, we previously analyzed different human cells by label-free quantitative mass spectrometry. The HeLa and HEK293 cells had been depleted of a certain component by siRNA or CRISPR/Cas9 treatment or were deficient patient fibroblasts and compared to the respective control cells by differential protein abundance analysis...
September 15, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37519262/rnf26-binds-perinuclear-vimentin-filaments-to-integrate-er-and-endolysosomal-responses-to-proteotoxic-stress
#6
JOURNAL ARTICLE
Tom Cremer, Lenard M Voortman, Erik Bos, Marlieke Lm Jongsma, Laurens R Ter Haar, Jimmy Jll Akkermans, Cami Mp Talavera Ormeño, Ruud Hm Wijdeven, Jelle de Vries, Robbert Q Kim, George Mc Janssen, Peter A van Veelen, Roman I Koning, Jacques Neefjes, Ilana Berlin
Proteotoxic stress causes profound endoplasmic reticulum (ER) membrane remodeling into a perinuclear quality control compartment (ERQC) for the degradation of misfolded proteins. Subsequent return to homeostasis involves clearance of the ERQC by endolysosomes. However, the factors that control perinuclear ER integrity and dynamics remain unclear. Here, we identify vimentin intermediate filaments as perinuclear anchors for the ER and endolysosomes. We show that perinuclear vimentin filaments engage the ER-embedded RING finger protein 26 (RNF26) at the C-terminus of its RING domain...
July 31, 2023: EMBO Journal
https://read.qxmd.com/read/37331602/lipid-biosynthesis-perturbation-impairs-endoplasmic-reticulum-associated-degradation
#7
JOURNAL ARTICLE
Samantha M Turk, Christopher J Indovina, Jacob M Miller, Danielle L Overton, Avery M Runnebohm, Cade J Orchard, Mary E Tragesser-Tiña, Samantha K Gosser, Ellen M Doss, Kyle A Richards, Courtney Broshar Irelan, Mahmoud M Daraghmi, Connor G Bailey, Julia M Niekamp, Kieran P Claypool, Sarah M Engle, Bryce W Buchanan, Kelsey A Woodruff, James B Olesen, Philip J Smaldino, Eric M Rubenstein
The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis...
June 16, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/37311770/tmx4-driven-linc-complex-disassembly-and-asymmetric-autophagy-of-the-nuclear-envelope-upon-acute-er-stress
#8
JOURNAL ARTICLE
Marika K Kucińska, Juliette Fedry, Carmela Galli, Diego Morone, Andrea Raimondi, Tatiana Soldà, Friedrich Förster, Maurizio Molinari
The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling...
June 13, 2023: Nature Communications
https://read.qxmd.com/read/37298528/the-3q-oncogene-sec62-predicts-response-to-neoadjuvant-chemotherapy-and-regulates-tumor-cell-migration-in-triple-negative-breast-cancer
#9
JOURNAL ARTICLE
Julia C Radosa, Mariz Kasoha, Merle Doerk, Annika Cullmann, Askin C Kaya, Maximilian Linxweiler, Marc P Radosa, Zoltan Takacs, Andrea Tirincsi, Sven Lang, Martin Jung, Julian Puppe, Barbara Linxweiler, Mathias Wagner, Rainer M Bohle, Erich-Franz Solomayer, Julia S M Zimmermann
In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62 , harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC...
May 31, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37164963/viral-subversion-of-selective-autophagy-is-critical-for-biogenesis-of-virus-replication-organelles
#10
JOURNAL ARTICLE
Yun Lan, Sophie Wilhelmina van Leur, Julia Ayano Fernando, Ho Him Wong, Martin Kampmann, Lewis Siu, Jingshu Zhang, Mingyuan Li, John M Nicholls, Sumana Sanyal
Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in virus production, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary...
May 10, 2023: Nature Communications
https://read.qxmd.com/read/37051023/editorial-the-evolving-picture-of-ca-2-leak-from-endoplasmic-reticulum-in-health-and-diseases
#11
EDITORIAL
Adolfo Cavalié, Richard Zimmermann
No abstract text is available yet for this article.
2023: Frontiers in Physiology
https://read.qxmd.com/read/37014697/repurposing-antipsychotic-drug-amisulpride-for-targeting-synovial-fibroblast-activation-in-arthritis
#12
JOURNAL ARTICLE
Dimitra Papadopoulou, Fani Roumelioti, Christos Tzaferis, Panagiotis Chouvardas, Anna-Kathrine Pedersen, Filippos Charalampous, Eleni Christodoulou-Vafeiadou, Lydia Ntari, Niki Karagianni, Maria C Denis, Jesper V Olsen, Alexis Ν Matralis, George Kollias
Synovial Fibroblasts (SFs) are key pathogenic drivers in Rheumatoid arthritis (RA). Their in vivo activation by TNF is sufficient to orchestrate full arthritic pathogenesis in animal models and TNF blockade proved efficacious for a high percentage of RA patients albeit co-inducing rare but serious side effects. Aiming to find new potent therapeutics, we applied the L1000CDS2 search engine, in order to repurpose drugs that could reverse the pathogenic expression signature of arthritogenic human TNF transgenic (hTNFtg) SFs...
April 4, 2023: JCI Insight
https://read.qxmd.com/read/36739418/vhl-hif-2%C3%AE-axis-induced-sema6a-upregulation-stabilized-%C3%AE-catenin-to-drive-clear-cell-renal-cell-carcinoma-progression
#13
JOURNAL ARTICLE
Jing Ji, Yuxin Xu, Mengru Xie, Xingbei He, Dexu Ren, Teng Qiu, Wenwen Liu, Zefeng Chen, Wen Shi, Zhen Zhang, Xiujun Wang, Weiling Wang, Jinming Ma, Qilan Qian, Aixin Jing, Xinhui Ma, Jingting Qin, Yuanyuan Ding, Ting Geng, Jiayan Yang, Zhichao Sun, Wei Liu, Shunfang Liu, Bin Liu
SEMA6A is a multifunctional transmembrane semaphorin protein that participates in various cellular processes, including axon guidance, cell migration, and cancer progression. However, the role of SEMA6A in clear cell renal cell carcinoma (ccRCC) is unclear. Based on high-throughput sequencing data, here we report that SEMA6A is a novel target gene of the VHL-HIF-2α axis and overexpressed in ccRCC. Chromatin immunoprecipitation and reporter assays revealed that HIF-2α directly activated SEMA6A transcription in hypoxic ccRCC cells...
February 4, 2023: Cell Death & Disease
https://read.qxmd.com/read/36359856/prp8-induced-circmaml2-facilitates-the-healing-of-the-intestinal-mucosa-via-recruiting-ptbp1-and-regulating-sec62
#14
JOURNAL ARTICLE
Yuequ Deng, Xiaoqing Xu, Fanze Meng, Jiaqi Lou, Yu Liao, Qi Li, Mengmeng Zhuang, Yong Sun
BACKGROUND: Multiple organ dysfunction syndrome (MODS) occurs in the gastrointestinal tract and injured intestinal mucosa is the anatomical basis for various diseases. The expression of circular RNAs (circRNAs) is implicated in many diseases; however, the role of circRNAs in intestinal mucosal injury is yet to be discovered. Our preliminary gene microarray analysis revealed a novel circular RNA, circMaml2, with a significant intestinal mucosal protection effect. Its expression was found to decrease in severely burned intestinal mucosal tissue, whereas its overexpression might facilitate the reconstruction of the injured intestinal mucous membrane...
November 1, 2022: Cells
https://read.qxmd.com/read/36262254/the-endoplasmic-reticulum-membrane-protein-sec62-as-potential-therapeutic-target-in-sec62-overexpressing-tumors
#15
REVIEW
Julia S M Zimmermann, Johannes Linxweiler, Julia C Radosa, Maximilian Linxweiler, Richard Zimmermann
The human SEC62 gene is located on chromosome 3q, was characterized as a tumor driver gene and is found to be overexpressed in an ever-growing number of tumors, particularly those with 3q26 amplification. Where analyzed, SEC62 overexpression was associated with poor prognosis. Sec62 protein is a membrane protein of the endoplasmic reticulum (ER) and has functions in endoplasmic reticulum protein import, endoplasmic reticulum-phagy and -in cooperation with the cytosolic protein calmodulin- the maintenance of cellular calcium homeostasis...
2022: Frontiers in Physiology
https://read.qxmd.com/read/36204309/what-makes-a-giant-fruit-assembling-a-genomic-toolkit-underlying-various-fruit-traits-of-the-mammoth-group-of-cucurbita-maxima
#16
JOURNAL ARTICLE
Umesh K Reddy, Purushothaman Natarajan, Venkata Lakshmi Abburi, Yan Tomason, Amnon Levi, Padma Nimmakayala
Since their introduction in Europe, pumpkins ( Cucurbita maxima Duch.) have rapidly dispersed throughout the world. This is mainly because of their wide genetic diversity and Plasticity to thrive in a wide range of geographical regions across the world, their high nutritional value and suitability to integrate with local cuisines, and their long shelf life. Competition for growing the showy type or mammoth-sized pumpkins that produce the largest fruit of the entire plant kingdom has drawn attention. In this study, we used genome-wide single nucleotide polymorphisms to resolve admixture among different pumpkin groups...
2022: Frontiers in Genetics
https://read.qxmd.com/read/36200182/endoplasmic-reticulum-resident-protein-sec62-drives-colorectal-cancer-metastasis-via-mapk-atf2-uca1-axis
#17
JOURNAL ARTICLE
Yirong Jin, Yuying Han, Suzhen Yang, Jiayi Cao, Mingzuo Jiang, Jie Liang
OBJECTIVE: Metastasis is responsible for the poor prognosis of patients with colorectal cancer (CRC), and the role of aberrant expression of endoplasmic reticulum (ER) receptors in tumour metastasis has not been fully elucidated. The aim of the study is to ensure the role of ER-resident protein Sec62 in CRC metastasis and illuminate associated molecular mechanisms. MATERIALS AND METHODS: Bioinformatics analysis, qRT-PCR, western blot and immunohistochemistry assays were performed to evaluate the expression level and clinical significance of Sec62 in CRC...
October 5, 2022: Cell Proliferation
https://read.qxmd.com/read/36162019/rolle-des-sec62-gens-in-der-dermatoonkologie-relevanz-f%C3%A3-r-die-tumorzellbiologie-prognoseeinsch%C3%A3-tzung-und-personalisierte-therapieplanung
#18
REVIEW
Maximilian Linxweiler, Cornelia S L Müller
No abstract text is available yet for this article.
September 2022: Journal der Deutschen Dermatologischen Gesellschaft: JDDG
https://read.qxmd.com/read/36122759/expression-level-of-sec62-modulates-membrane-insertion-of-marginally-hydrophobic-segments
#19
JOURNAL ARTICLE
Sung-Jun Jung, Mekang Yun, Chewon Yim, Sujin Hong, Won-Ki Huh, Hyun Kim
In the endoplasmic reticulum (ER) membrane, transmembrane (TM) domain insertion occurs through the Sec61 channel with its auxiliary components, including Sec62. Sec62 interacts with the Sec61 channel and is located on the front side of the Sec61 lateral gate, an entry site for TM domains to the lipid bilayer. Overexpression of Sec62 led to a growth defect in yeast, and we investigated its effects on protein translocation and membrane insertion by pulse labeling of Sec62 client proteins. Our data show that the insertion efficiency of marginally hydrophobic TM segments is reduced upon Sec62 overexpression...
September 17, 2022: Biochimica et Biophysica Acta. Biomembranes
https://read.qxmd.com/read/36116515/effect-of-sec62-on-the-conformation-of-the-sec61-channel-in-yeast
#20
JOURNAL ARTICLE
Pratiti Bhadra, Karin Römisch, Volkhard Helms
Most eukaryotic secretory and membrane proteins are funneled by the Sec61 complex into the secretory pathway. Furthermore, some substrate peptides rely on two essential accessory proteins, Sec62 and Sec63, being present to assist with their translocation via the Sec61 channel in post-translational translocation. Cryo-electron microscopy (cryo-EM) recently succeeded in determining atomistic structures of unbound and signal sequence-engaged Sec complexes from Saccharomyces cerevisiae, involving the Sec61 channel and the proteins Sec62, Sec63, Sec71 and Sec72...
September 15, 2022: Biochimica et Biophysica Acta. Biomembranes
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