FEBS JournalPub Date : 2022-11-01DOI: 10.1111/febs.15894
Junko Tomikawa, Kei Miyamoto
{"title":"Structural alteration of the nucleus for the reprogramming of gene expression.","authors":"Junko Tomikawa, Kei Miyamoto","doi":"10.1111/febs.15894","DOIUrl":"https://doi.org/10.1111/febs.15894","url":null,"abstract":"<p><p>The regulation of gene expression is a critical process for establishing and maintaining cellular identity. Gene expression is controlled through a chromatin-based mechanism in the nucleus of eukaryotic cells. Recent studies suggest that chromatin accessibility and the higher-order structure of chromatin affect transcriptional outcome. This is especially evident when cells change their fate during development and nuclear reprogramming. Furthermore, non-chromosomal contents of the cell nucleus, namely nucleoskeleton proteins, can also affect chromatin and nuclear structures, resulting in transcriptional alterations. Here, we review our current mechanistic understanding about how chromatin and nuclear structures impact transcription in the course of embryonic development, cellular differentiation and nuclear reprogramming, and also discuss unresolved questions that remain to be addressed in the field.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10865849","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 : 2022-11-01DOI: 10.1111/febs.16018
Daniela Intartaglia, Giuliana Giamundo, Ivan Conte
{"title":"Autophagy in the retinal pigment epithelium: a new vision and future challenges.","authors":"Daniela Intartaglia, Giuliana Giamundo, Ivan Conte","doi":"10.1111/febs.16018","DOIUrl":"https://doi.org/10.1111/febs.16018","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) is a highly specialized monolayer of polarized, pigmented epithelial cells that resides between the vessels of the choriocapillaris and the neural retina. The RPE is essential for the maintenance and survival of overlying light-sensitive photoreceptors, as it participates in the formation of the outer blood-retinal barrier, phagocytosis, degradation of photoreceptor outer segment (POS) tips, maintenance of the retinoid cycle, and protection against light and oxidative stress. Autophagy is an evolutionarily conserved 'self-eating' process, designed to maintain cellular homeostasis. The daily autophagy demands in the RPE require precise gene regulation for the digestion and recycling of intracellular and POS components in lysosomes in response to light and stress conditions. In this review, we discuss selective autophagy and focus on the recent advances in our understanding of the mechanism of cell clearance in the RPE for visual function. Understanding how this catabolic process is regulated by both transcriptional and post-transcriptional mechanisms in the RPE will promote the recognition of pathological pathways in genetic disease and shed light on potential therapeutic strategies to treat visual impairments in patients with retinal disorders associated with lysosomal dysfunction.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.16018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2022-11-01DOI: 10.1111/febs.16281
Saori Noguchi, Shigeomi Shimizu
{"title":"Molecular mechanisms and biological roles of GOMED.","authors":"Saori Noguchi, Shigeomi Shimizu","doi":"10.1111/febs.16281","DOIUrl":"https://doi.org/10.1111/febs.16281","url":null,"abstract":"<p><p>We previously discovered an autophagy-like proteolysis mechanism that uses the Golgi membrane, namely, Golgi membrane-associated degradation (GOMED). Morphologically, GOMED resembles canonical autophagy, but the two mechanisms have different cellular functions, as they degrade different substrates and use different membrane sources. Furthermore, although the molecules involved partially overlap, the core molecules are completely different. GOMED preferentially degrades Golgi-trafficking proteins, including insulin granules in pancreatic β-cells and ceruloplasmin in neurons, and is involved in a wide variety of physiological events.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520713","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 : 2022-11-01DOI: 10.1111/febs.16125
Michael Rangel, Jerry Kong, Vrushank Bhatt, Khoosheh Khayati, Jessie Yanxiang Guo
{"title":"Autophagy and tumorigenesis.","authors":"Michael Rangel, Jerry Kong, Vrushank Bhatt, Khoosheh Khayati, Jessie Yanxiang Guo","doi":"10.1111/febs.16125","DOIUrl":"https://doi.org/10.1111/febs.16125","url":null,"abstract":"<p><p>Autophagy is a catabolic process that captures cellular waste and degrades them in the lysosome. The main functions of autophagy are quality control of cytosolic proteins and organelles, and intracellular recycling of nutrients in order to maintain cellular homeostasis. Autophagy is upregulated in many cancers to promote cell survival, proliferation, and metastasis. Both cell-autonomous autophagy (also known as tumor autophagy) and non-cell-autonomous autophagy (also known as host autophagy) support tumorigenesis through different mechanisms, including inhibition of p53 activation, sustaining redox homeostasis, maintenance of essential amino acids levels in order to support energy production and biosynthesis, and inhibition of antitumor immune responses. Therefore, autophagy may serve as a tumor-specific vulnerability and targeting autophagy could be a novel strategy in cancer treatment.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.16125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9231134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2022-11-01DOI: 10.1111/febs.16183
Shunbang Yu, Li Yu
{"title":"Migrasome biogenesis and functions.","authors":"Shunbang Yu, Li Yu","doi":"10.1111/febs.16183","DOIUrl":"https://doi.org/10.1111/febs.16183","url":null,"abstract":"<p><p>The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate-like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.16183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS JournalPub Date : 2022-11-01DOI: 10.1111/febs.16117
İbrahim Avşar Ilık, Tuğçe Aktaş
{"title":"Nuclear speckles: dynamic hubs of gene expression regulation.","authors":"İbrahim Avşar Ilık, Tuğçe Aktaş","doi":"10.1111/febs.16117","DOIUrl":"https://doi.org/10.1111/febs.16117","url":null,"abstract":"<p><p>Complex, multistep biochemical reactions that routinely take place in our cells require high concentrations of enzymes, substrates, and other structural components to proceed efficiently and typically require chemical environments that can inhibit other reactions in their immediate vicinity. Eukaryotic cells solve these problems by restricting such reactions into diffusion-restricted compartments within the cell called organelles that can be separated from their environment by a lipid membrane, or into membrane-less compartments that form through liquid-liquid phase separation (LLPS). One of the most easily noticeable and the earliest discovered organelle is the nucleus, which harbors the genetic material in cells where transcription by RNA polymerases produces most of the messenger RNAs and a plethora of noncoding RNAs, which in turn are required for translation of mRNAs in the cytoplasm. The interior of the nucleus is not a uniform soup of biomolecules and rather consists of a variety of membrane-less bodies, such as the nucleolus, nuclear speckles (NS), paraspeckles, Cajal bodies, histone locus bodies, and more. In this review, we will focus on NS with an emphasis on recent developments including our own findings about the formation of NS by two large IDR-rich proteins SON and SRRM2.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.16117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516344","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 : 2022-04-01Epub Date: 2022-01-03DOI: 10.1111/febs.16335
Karl J Kunert, Priyen Pillay
{"title":"Loop replacement design: a new way to improve potency of plant cystatins.","authors":"Karl J Kunert, Priyen Pillay","doi":"10.1111/febs.16335","DOIUrl":"https://doi.org/10.1111/febs.16335","url":null,"abstract":"<p><p>Plant cystatins function as competitive inhibitors of cysteine proteases. Similar to other defence proteins, cystatins include hypervariable, positively selected amino acid sites presumably impacting their biological activity. Protein engineering approaches, such as point mutations, at these functionally relevant amino acid sites have already been found to be a powerful tool in improving the inhibitory properties of cystatins. Such engineered cystatins not only better protect against digestive proteases of herbivorous arthropods but also against cysteine proteases of several other plant pests as well as against cysteine proteases produced in plant during stress-induced senescence. Despite previous engineering successes, an urgent need still exists to further improve both plant cystatin potency and specificity. Tremblay and colleagues propose in this issue a new cystatin engineering strategy to substitute the function-related structural elements (SEs) of a cystatin by the corresponding elements of an alternative cystatin. This strategy, possibly combined with direct cystatin gene editing in a target plant, might provide an innovative way to control cysteine protease activity. Comment on https://doi.org/10.1111/febs.16288.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39781364","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 : 2022-04-01Epub Date: 2021-03-22DOI: 10.1111/febs.15817
Tamra E Werbowetski-Ogilvie
{"title":"From sorting to sequencing in the molecular era: the evolution of the cancer stem cell model in medulloblastoma.","authors":"Tamra E Werbowetski-Ogilvie","doi":"10.1111/febs.15817","DOIUrl":"https://doi.org/10.1111/febs.15817","url":null,"abstract":"<p><p>The cancer stem cell (CSC) model posits that tumors contain subpopulations that display defining features of normal stem cells including self-renewal capacity and differentiation. Tumor cells exhibiting these features are now considered to be responsible for tumor propagation and drug resistance in a wide variety of cancers. Therefore, the identification of robust CSC markers and characterization of CSC-specific molecular signatures may lead to the identification of novel therapeutics that selectively abolish this clinically relevant cell population while preserving normal tissue. Brain tumor researchers have been at the forefront of the CSC field. From initial in vitro cell sorting experiments to the sophisticated bioinformatic technologies that now exquisitely resolve primary brain tumors at a single-cell level, recent glioma and medulloblastoma (MB) studies have integrated developmental state with genomic and transcriptome data to identify the spectrum of cell types that may drive tumor progression. This review will examine the last two decades of CSC studies in the field. Seminal discoveries, emerging controversies, and outstanding questions will be covered with a particular focus on MB, the most common malignant primary brain tumor in children.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/febs.15817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25472001","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 : 2022-04-01Epub Date: 2021-12-07DOI: 10.1111/febs.16293
Henna Zahid, Andy M Lau, Sharon M Kelly, Kersti Karu, Jayesh Gor, Stephen J Perkins, Lindsay C McDermott
{"title":"Identification of diverse lipid-binding modes in the groove of zinc α<sub>2</sub> glycoprotein reveals its functional versatility.","authors":"Henna Zahid, Andy M Lau, Sharon M Kelly, Kersti Karu, Jayesh Gor, Stephen J Perkins, Lindsay C McDermott","doi":"10.1111/febs.16293","DOIUrl":"https://doi.org/10.1111/febs.16293","url":null,"abstract":"<p><p>ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C<sub>11</sub> fatty acid, DAUDA, differently to the boron dipyrromethane C<sub>16</sub> fatty acid, C<sub>16</sub> -BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C<sub>16</sub> -BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related Cluster of differentiation 1 proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C<sub>16</sub> -BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C<sub>16</sub> -BODIPY but not of DAUDA compared to wild-type ZAG and showed that C<sub>16</sub> -BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C<sub>16</sub> -BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C<sub>16</sub> -BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand.</p>","PeriodicalId":12261,"journal":{"name":"FEBS Journal","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39655072","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}