FEBS JournalPub Date : 2021-08-06DOI: 10.1111/FEBS.16209/V2/RESPONSE1
K. Luo, R. Stocker, W. Britton, Kazu Kikuchi, Stefan H. Oehlers
{"title":"Author response for \"Heme oxygenase limits Mycobacterium marinum infection‐induced detrimental ferrostatin‐sensitive cell death in zebrafish\"","authors":"K. Luo, R. Stocker, W. Britton, Kazu Kikuchi, Stefan H. Oehlers","doi":"10.1111/FEBS.16209/V2/RESPONSE1","DOIUrl":"https://doi.org/10.1111/FEBS.16209/V2/RESPONSE1","url":null,"abstract":"","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2021-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83312087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2021-08-03DOI: 10.1111/febs.16184/v2/review1
K. Thakur
{"title":"Review for \"Structural basis of an epitope tagging system derived from Haloarcula marismortui bacteriorhodopsin I D94N and its monoclonal antibody GD‐26\"","authors":"K. Thakur","doi":"10.1111/febs.16184/v2/review1","DOIUrl":"https://doi.org/10.1111/febs.16184/v2/review1","url":null,"abstract":"","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"13 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75434174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2021-08-01Epub Date: 2021-02-22DOI: 10.1111/febs.15748
Pedro do Couto Bordignon, Sebastian Pechmann
{"title":"Inferring translational heterogeneity from Saccharomyces cerevisiae ribosome profiling.","authors":"Pedro do Couto Bordignon, Sebastian Pechmann","doi":"10.1111/febs.15748","DOIUrl":"https://doi.org/10.1111/febs.15748","url":null,"abstract":"<p><p>Translation of mRNAs into proteins by the ribosome is the most important step of protein biosynthesis. Accordingly, translation is tightly controlled and heavily regulated to maintain cellular homeostasis. Ribosome profiling (Ribo-seq) has revolutionized the study of translation by revealing many of its underlying mechanisms. However, equally many aspects of translation remain mysterious, in part also due to persisting challenges in the interpretation of data obtained from Ribo-seq experiments. Here, we show that some of the variability observed in Ribo-seq data has biological origins and reflects programmed heterogeneity of translation. Through a comparative analysis of Ribo-seq data from Saccharomyces cerevisiae, we systematically identify short 3-codon sequences that are differentially translated (DT) across mRNAs, that is, identical sequences that are translated sometimes fast and sometimes slowly beyond what can be attributed to variability between experiments. Remarkably, the thus identified DT sequences link to mechanisms known to regulate translation elongation and are enriched in genes important for protein and organelle biosynthesis. Our results thus highlight examples of translational heterogeneity that are encoded in the genomic sequences and tuned to optimizing cellular homeostasis. More generally, our work highlights the power of Ribo-seq to understand the complexities of translation regulation.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4541-4559"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15748","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25332254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A glaucoma- and ALS-associated mutant of OPTN induces neuronal cell death dependent on Tbk1 activity, autophagy and ER stress.","authors":"Swetha Medchalmi, Priyanka Tare, Zuberwasim Sayyad, Ghanshyam Swarup","doi":"10.1111/febs.15752","DOIUrl":"https://doi.org/10.1111/febs.15752","url":null,"abstract":"<p><p>Mutations in OPTN are associated with glaucoma, an eye disease, and also with amyotrophic lateral sclerosis (ALS), a motor neuron disease. A 2-bp insertion in OPTN (691_692insAG or 2bpIns-OPTN) is associated with both glaucoma and ALS. This mutation results in frame shift after 127 amino acids, giving rise to a protein with C-terminal aberrant sequence. We have explored the mechanism of induction of cell death by this mutant in a motor neuron cell line, NSC-34, and also in a retinal cell line, 661W. Compared to wild-type OPTN, this mutant induced more cell death in NSC-34 and 661W cells. This mutant localizes predominantly in the nucleus whereas normal OPTN localizes in the cytoplasm. Deletion analysis of 2bpIns-OPTN showed that the aberrant sequence was not essential for cell death induction. This mutant interacts with TANK-binding kinase 1 (Tbk1) but not with OPTN and activates Tbk1. This mutant induced ER stress in NSC-34 cells as seen by induction of C/EBP homologous protein (CHOP) and some other genes. Induction of CHOP, autophagosomal protein LC3-II and cell death by this mutant were abrogated by Tbk1 knockdown and also by 4-phenylbutyric acid, that inhibits ER stress. Induction of CHOP and cell death by 2bpIns-OPTN was autophagy dependent as shown by the effect of Atg5 knockdown. This mutant caused increased formation of LC3-positive aggregates. Treatment of cells with autophagy inducer rapamycin reduced LC3-positive aggregates, CHOP and cell death induced by 2bpIns-OPTN. These results suggest that constitutive activation of Tbk1 by 2bpIns-OPTN leads to impaired autophagy that results in ER stress and cell death.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4576-4595"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15752","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25337650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2021-08-01DOI: 10.1111/febs.15891
Nikos Karamanos
{"title":"Editor Profile: Nikos Karamanos.","authors":"Nikos Karamanos","doi":"10.1111/febs.15891","DOIUrl":"https://doi.org/10.1111/febs.15891","url":null,"abstract":"<p><p>In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Nikos Karamanos is Professor of Biochemistry in the Department of Chemistry, University of Patras in Greece. He joined the editorial board of The FEBS Journal in 2020, having previously served on the advisory board for several years.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4442-4444"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39270030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Crystal structure of the full-length LysR-type transcription regulator CbnR in complex with promoter DNA.","authors":"Evdokia-Anastasia Giannopoulou, Miki Senda, Maharani Pertiwi Koentjoro, Naruhiko Adachi, Naoto Ogawa, Toshiya Senda","doi":"10.1111/febs.15764","DOIUrl":"https://doi.org/10.1111/febs.15764","url":null,"abstract":"<p><p>LysR-type transcription regulators (LTTRs) comprise one of the largest families of transcriptional regulators in bacteria. They are typically homo-tetrameric proteins and interact with promoter DNA of ~ 50-60 bp. Earlier biochemical studies have suggested that LTTR binding to promoter DNA bends the DNA and, upon inducer binding, the bend angle of the DNA is reduced through a quaternary structure change of the tetrameric LTTR, leading to the activation of transcription. To date, crystal structures of full-length LTTRs, DNA-binding domains (DBD) with their target DNAs, and the regulatory domains with and without inducer molecules have been reported. However, these crystal structures have not provided direct evidence of the quaternary structure changes of LTTRs or of the molecular mechanism underlying these changes. Here, we report the first crystal structure of a full-length LTTR, CbnR, in complex with its promoter DNA. The crystal structure showed that, in the absence of bound inducer molecules, the four DBDs of the tetrameric CbnR interact with the promoter DNA, bending the DNA by ~ 70°. Structural comparison between the DNA-free and DNA-bound forms demonstrates that the quaternary structure change of the tetrameric CbnR required for promoter region-binding arises from relative orientation changes of the three domains in each subunit. The mechanism of the quaternary structure change caused by inducer binding is also discussed based on the present crystal structure, affinity analysis between CbnR and the promoter DNA, and earlier mutational studies on CbnR. DATABASE: Atomic coordinates and structure factors for the full-length Cupriavidus necator NH9 CbnR in complex with promoter DNA are available in the Protein Data Bank under the accession code 7D98.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4560-4575"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25360617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2021-08-01Epub Date: 2021-03-05DOI: 10.1111/febs.15778
Moran Shalev, Esther Arman, Merle Stein, Yael Cohen-Sharir, Vlad Brumfeld, Sergey Kapishnikov, Isabelle Royal, Jan Tuckermann, Ari Elson
{"title":"PTPRJ promotes osteoclast maturation and activity by inhibiting Cbl-mediated ubiquitination of NFATc1 in late osteoclastogenesis.","authors":"Moran Shalev, Esther Arman, Merle Stein, Yael Cohen-Sharir, Vlad Brumfeld, Sergey Kapishnikov, Isabelle Royal, Jan Tuckermann, Ari Elson","doi":"10.1111/febs.15778","DOIUrl":"https://doi.org/10.1111/febs.15778","url":null,"abstract":"<p><p>Bone-resorbing osteoclasts (OCLs) are multinucleated phagocytes, whose central roles in regulating bone formation and homeostasis are critical for normal health and development. OCLs are produced from precursor monocytes in a multistage process that includes initial differentiation, cell-cell fusion, and subsequent functional and morphological maturation; the molecular regulation of osteoclastogenesis is not fully understood. Here, we identify the receptor-type protein tyrosine phosphatase PTPRJ as an essential regulator specifically of OCL maturation. Monocytes from PTPRJ-deficient (JKO) mice differentiate and fuse normally, but their maturation into functional OCLs and their ability to degrade bone are severely inhibited. In agreement, mice lacking PTPRJ throughout their bodies or only in OCLs exhibit increased bone mass due to reduced OCL-mediated bone resorption. We further show that PTPRJ promotes OCL maturation by dephosphorylating the M-CSF receptor (M-CSFR) and Cbl, thus reducing the ubiquitination and degradation of the key osteoclastogenic transcription factor NFATc1. Loss of PTPRJ increases ubiquitination of NFATc1 and reduces its amounts at later stages of osteoclastogenesis, thereby inhibiting OCL maturation. PTPRJ thus fulfills an essential and cell-autonomous role in promoting OCL maturation by balancing between the pro- and anti-osteoclastogenic activities of the M-CSFR and maintaining NFATc1 expression during late osteoclastogenesis.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4702-4723"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25384271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2021-08-01DOI: 10.1111/febs.15890
The Febs Journal Editorial Team, Hyunsook Lee
{"title":"Editor Profile: Hyunsook Lee.","authors":"The Febs Journal Editorial Team, Hyunsook Lee","doi":"10.1111/febs.15890","DOIUrl":"https://doi.org/10.1111/febs.15890","url":null,"abstract":"<p><p>In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Hyunsook Lee is Professor at the Laboratory of Cancer Cell Biology at Seoul National University in Korea. She has served as an editorial board member of The FEBS Journal since 2018.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4439-4441"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39270029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Constitutive activity of GPR26 regulated by ubiquitin-dependent degradation and its antitumor role.","authors":"Fang Liu, Wei Yang, Minghui Hu, Yong Zhang, Beicheng Sun, Hao Yang, Juergen Brosius, Cheng Deng","doi":"10.1111/febs.15763","DOIUrl":"https://doi.org/10.1111/febs.15763","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) play important roles in many physiological functions and numerous diseases. In addition to the classic ligand-stimulated receptor activity, an increasing number of studies have established that many GPCRs function constitutively in a receptor dose-dependent manner. Previous observations showed that following gene transfection, little or no protein was detectable for certain GPCRs (designated apparent state A), such as GPR26, GPR39, GPR78, GPR133, GPR139, BRS3, and LGR5, which showed strong constitutive activities. When we lysed cells in the immediate presence of western blot loading buffer, a significant increase of protein levels was detected (actual state B), which was much closer to the true expression levels under physiological conditions. GPR26 was chosen for further functional experiments as the actual state B. We identified an important ubiquitination site, K286, as well as the ubiquitin ligase E3 homologous to the E6-associated protein carboxyl terminus domain containing 3 interacting with GPR26. The pronounced differences in the protein expression and constitutive activity of GPR26 were a consequence of the ubiquitin-mediated rapid degradation mechanism. Furthermore, we identified in vitro and in vivo antitumor activity associated with high expression levels and constitutive activity of GPR26 in liver cancer cells. Hence, GPR26 could act as an antitumor gene for hepatocellular carcinoma. This study also represents the actual state B of a batch of GPCRs that actually play potentially important roles in physiological functions by their constitutive activity, which is controlled by rapid ubiquitin-dependent degradation.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":"288 15","pages":"4655-4682"},"PeriodicalIF":5.4,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25361977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}