Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"Alzheimer's disease-associated mutant ubiquitin (UBB+1) is secreted through an autophagosome-like vesicle-mediated unconventional pathway","authors":"Ajay R. Wagh,&nbsp;Prasad Sulakshane,&nbsp;Michael H. Glickman","doi":"10.1016/j.bbagrm.2023.194936","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2023.194936","url":null,"abstract":"<div><p><span>Misfolded protein aggregation at both intracellular and extracellular milieus is thought to be the major etiology of Alzheimer's disease (AD). UBB</span>⁺¹, a frameshift variant of the ubiquitin B gene (UBB) results in a folded ubiquitin domain fused to a flexible unstructured extension. Accumulation of UBB⁺¹ in extracellular plaques in the brains of AD patients undoubtedly suggests a role of the ubiquitin-proteasome system in AD. However, the exact mechanism of extracellular secretion of UBB⁺¹ remains unknown.</p><p>In an attempt to understand the molecular mechanism of UBB⁺¹<span> secretion, we performed a survey of secretory pathways and identified the involvement of unconventional autophagosome-mediated UBB</span>⁺¹ secretion. Expression of UBB⁺¹<span><span> was sufficient to stimulate LC3B/Atg8 conversion from LC3B-I to LC3B-II, which indicates initiation of the autophagy pathway. Furthermore, deficiency of ATG5 - a key player in </span>autophagosome formation - inhibited UBB</span>⁺¹ secretion. Based on immunofluorescence 3D structured illumination (SIM) microscopy and co-immunoprecipitation, we provide evidence that UBB⁺¹<span> is associated with the secretory autophagosome marker, SEC22B, while HSP90 possibly acts as a carrier. Using LC-MS/MS and mutagenesis we found that in cells, UBB</span>⁺¹<span><span><span> is ubiquitinated on lysine 11, 29, and 48, however, this ubiquitination does not contribute to its secretion. By contrast, </span>proteasome or </span>lysosome inhibition slightly enhanced secretion. Taken together, this study suggests that by ridding cells of UBB</span>⁺¹, secretory autophagosomes may alleviate the cellular stress associated with UBB⁺¹, yet simultaneously mediate the spreading of a mutant specie with disordered characteristics to the extracellular milieu.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194936"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49865123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin4 impacts mitochondrial homeostasis in pancreatic cancer cells by reducing the stability of AlkB homolog 1 via deacetylation of the HRD1-SEL1L complex","authors":"Dongnan Ping ,&nbsp;Xiaofan Pu ,&nbsp;Guoping Ding ,&nbsp;Chaolei Zhang ,&nbsp;Junbin Jin ,&nbsp;Chengjie Xu ,&nbsp;Jiazheng Liu ,&nbsp;Shengnan Jia ,&nbsp;Liping Cao","doi":"10.1016/j.bbagrm.2023.194941","DOIUrl":"10.1016/j.bbagrm.2023.194941","url":null,"abstract":"<div><p><span><span><span>Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a poor prognosis. As a tumor inhibitor, the specific tumor suppressor mechanism of Sirtuin4(SIRT4) in PDAC remains elusive. In this study, SIRT4 was found to inhibit PDAC by impacting mitochondrial </span>homeostasis. SIRT4 deacetylated lysine 547 of SEL1L and increased the protein level of an E3 </span>ubiquitin ligase<span> HRD1. As a central member of ER-associated protein degradation (ERAD), HRD1-SEL1L complex is recently reported to regulate the mitochondria, though the mechanism is not fully delineated. Here, we found the increase in SEL1L-HRD1 complex decreased the stability of a mitochondrial protein, ALKBH1. Downregulation of ALKBH1 subsequently blocked the transcription of mitochondrial DNA-coded genes, and resulted in mitochondrial damage. Lastly, a putative SIRT4 stimulator, Entinostat, was identified, which upregulated the expression of SIRT4 and effectively inhibited pancreatic cancer </span></span><em>in vivo</em> and <em>in vitro</em>.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194941"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced gene regulation by cooperation between mRNA decay and gene transcription","authors":"José García-Martínez ,&nbsp;Abhyudai Singh ,&nbsp;Daniel Medina ,&nbsp;Sebastián Chávez ,&nbsp;José E. Pérez-Ortín","doi":"10.1016/j.bbagrm.2023.194910","DOIUrl":"10.1016/j.bbagrm.2023.194910","url":null,"abstract":"<div><p>It has become increasingly clear in the last few years that gene expression in eukaryotes is not a linear process from mRNA synthesis in the nucleus to translation and degradation in the cytoplasm, but works as a circular one where the mRNA level is controlled by crosstalk between nuclear transcription and cytoplasmic decay pathways. One of the consequences of this crosstalk is the approximately constant level of mRNA. This is called mRNA buffering and happens when transcription and mRNA degradation act at compensatory rates. However, if transcription and mRNA degradation act additively, enhanced gene expression regulation occurs. In this work, we analyzed new and previously published genomic datasets obtained for several yeast mutants related to either transcription or mRNA decay that are not known to play any role in the other process. We show that some, which were presumed only transcription factors (Sfp1) or only decay factors (Puf3, Upf2/3), may represent examples of RNA-binding proteins (RBPs) that make specific crosstalk to enhance the control of the mRNA levels of their target genes by combining additive effects on transcription and mRNA stability. These results were mathematically modeled to see the effects of RBPs when they have positive or negative effects on mRNA synthesis and decay rates. We found that RBPs can be an efficient way to buffer or enhance gene expression responses depending on their respective effects on transcription and mRNA stability.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194910"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone H4K20 monomethylation enables recombinant nucleosome methylation by PRMT1 in vitro","authors":"Alice Shi Ming Li ,&nbsp;Charles Homsi ,&nbsp;Eric Bonneil ,&nbsp;Pierre Thibault ,&nbsp;Alain Verreault ,&nbsp;Masoud Vedadi","doi":"10.1016/j.bbagrm.2023.194922","DOIUrl":"10.1016/j.bbagrm.2023.194922","url":null,"abstract":"<div><p><span><span>Protein arginine methyltransferases<span> (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of histones and nonhistone proteins. There are nine members in the PRMT family (PRMT1 to PRMT9), and </span></span>PRMT1<span> is a dominant member catalyzing majority of arginine methylation in the cell. However, none of the PRMTs is active with recombinant nucleosome as substrate </span></span><em>in vitro</em><span>. Here, we report the discovery of the first in class novel crosstalk between histone H4 lysine 20 (H4K20) monomethylation on nucleosome by SETD8 and histone H4 arginine 3 (H4R3) methylation by PRMT1 </span><em>in vitro</em>. Full kinetic characterization and mass spectrometry analysis indicated that PRMT1 is only active with recombinant nucleosomes monomethylated at H4K20 by SETD8. These data suggests that the level of activity of PRMT1 could potentially be regulated selectively by SETD8 in various pathways, providing a new approach for discovery of selective regulators of PRMT1 activity.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194922"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLI1, a novel target of the ER stress regulator p97/VCP, promotes ATF6f-mediated activation of XBP1","authors":"Luciana L. Almada ,&nbsp;Kim Barroso ,&nbsp;Sandhya Sen ,&nbsp;Murat Toruner ,&nbsp;Ashley N. Sigafoos ,&nbsp;Glancis L. Raja Arul ,&nbsp;David R. Pease ,&nbsp;Renzo E. Vera ,&nbsp;Rachel L.O. Olson ,&nbsp;Holger W. Auner ,&nbsp;Rémy Pedeux ,&nbsp;Juan L. Iovanna ,&nbsp;Eric Chevet ,&nbsp;Martin E. Fernandez-Zapico","doi":"10.1016/j.bbagrm.2023.194924","DOIUrl":"10.1016/j.bbagrm.2023.194924","url":null,"abstract":"<div><p><span><span><span>Upon accumulation of improperly folded proteins in the Endoplasmic Reticulum (ER), the Unfolded Protein Response<span> (UPR) is triggered to restore ER homeostasis<span>. The induction of stress genes is a sine qua non condition for effective adaptive UPR. Although this requirement has been extensively described, the mechanisms underlying this process remain in part uncharacterized. Here, we show that p97/VCP, an AAA+ ATPase known to contribute to ER stress-induced gene expression, regulates the transcription factor </span></span></span>GLI1, a primary effector of Hedgehog (Hh) signaling. Under basal (non-ER stress) conditions, GLI1 is repressed by a p97/VCP-HDAC1 complex while upon </span>ER stress<span> GLI1 is induced through a mechanism requiring both USF2 binding and increase </span></span>histone acetylation<span><span> at its promoter. Interestingly, the induction of GLI1 was independent of ligand-regulated Hh signaling. Further analysis showed that GLI1 cooperates with ATF6f to induce promoter activity and expression of XBP1, a key transcription factor driving UPR. Overall, our work demonstrates a novel role for GLI1 in the regulation of ER stress gene expression and defines the interplay between p97/VCP, </span>HDAC1 and USF2 as essential players in this process.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194924"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel splice variants of LINC00963 suppress colorectal cancer cell proliferation via miR-10a/miR-143/miR-217/miR-512-mediated regulation of PI3K/AKT and Wnt/β-catenin signaling pathways","authors":"Zahra Ghaemi,&nbsp;Seyed Javad Mowla,&nbsp;Bahram Mohammad Soltani","doi":"10.1016/j.bbagrm.2023.194921","DOIUrl":"10.1016/j.bbagrm.2023.194921","url":null,"abstract":"<div><p><span><span><span><span>Emerging evidence has shown lncRNAs play important roles in </span>signaling pathways involved in colorectal cancer (CRC) carcinogenesis. However, only a few functional lncRNAs have been extensively researched, especially in CRC-related signaling pathways. Looking for novel candidate regulators of CRC incidence and progression, using available RNA-seq and microarray datasets, LINC00963 was introduced as a bona fide oncogenic-lncRNA. Consistently, RT-qPCR results showed that LINC00963 was up-regulated in CRC tissues. However, our attempt to amplify the full-length lncRNA from cDNA resulted in the discovery of two novel variants (LINC00963-v2 &amp; LINC00963-v3) that surprisingly, were downregulated in CRC tissues, detected by RT-qPCR. Overexpression of LINC00963-v2/-v3 in HCT116 and SW480 cells resulted in downregulation of the major </span>oncogenes and upregulation of the main </span>tumor suppressor genes<span> involved in PI3K and Wnt signaling<span>, verified through RT-qPCR, western blotting, and TOPFlash assays. Mechanistic studies revealed that LINC00963-v2/-v3 exert their effect on PI3K and Wnt signaling through sponging miR-10a-5p, miR-143-3p, miR-217, and miR-512-3p, which in turn these miRNAs are fine-regulators of </span></span></span><em>PTEN</em>, <em>APC1</em>, and <em>Axin1</em><span> tumor suppressor<span><span> genes verified by dual-luciferase assay and RT-qPCR. At cellular levels, LINC00963-v2/-v3 overexpression suppressed cell proliferation, viability, and migration while increasing the apoptosis of CRC cell lines, detected by </span>PI flow cytometry, colony formation, MTT, RT-qPCR, wound-healing, Transwell, AnnexinV-PE/7AAD, caspase3/7 activity assays, and Hoechst/PI-AO/EB staining. Overall, our results indicate that LINC00963-v2 &amp; -v3 are novel tumor suppressor ceRNAs that attenuate the PI3K and Wnt pathways during CRC incidence and these lncRNAs may serve as potential targets for CRC therapy.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194921"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic approaches to study ubiquitinomics","authors":"Indrajit Sahu ,&nbsp;He Zhu ,&nbsp;Sara J. Buhrlage ,&nbsp;Jarrod A. Marto","doi":"10.1016/j.bbagrm.2023.194940","DOIUrl":"10.1016/j.bbagrm.2023.194940","url":null,"abstract":"<div><p><span>As originally described some 40 years ago, protein ubiquitination was thought to serve primarily as a static mark for </span>protein degradation<span>. In the ensuing years, it has become clear that ‘ubiquitination’ is a structurally diverse and dynamic post-translational modification and is intricately involved in a myriad of signaling pathways<span> in all eukaryote cells. And like other key pathways in the functional proteome<span>, ubiquitin signaling is often disrupted, sometimes severely so, in human pathophysiology. As a result of its central role in normal physiology and human disease, the ubiquitination field is now represented across the full landscape of biomedical research from fundamental structural and biochemical studies to translational and clinical research. In recent years, mass spectrometry has emerged as a powerful technology for the detection and characterization of protein ubiquitination. Herein we detail qualitative and quantitative proteomic methods using a compare/contrast approach to highlight their strengths and weaknesses.</span></span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194940"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SAGA HAT module is tethered by its SWIRM domain and modulates activity of the SAGA DUB module","authors":"Sara T. Haile ,&nbsp;Sanim Rahman ,&nbsp;James K. Fields ,&nbsp;Benjamin C. Orsburn ,&nbsp;Namandjé N. Bumpus ,&nbsp;Cynthia Wolberger","doi":"10.1016/j.bbagrm.2023.194929","DOIUrl":"10.1016/j.bbagrm.2023.194929","url":null,"abstract":"<div><p>The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is a transcriptional co-activator that both acetylates and deubiquitinates histones. The histone acetyltransferase (HAT) subunit, Gcn5, is part of a subcomplex of SAGA called the HAT module. A minimal HAT module complex containing Gcn5 bound to Ada2 and Ada3 is required for full Gcn5 activity on nucleosomes. Deletion studies have suggested that the Ada2 SWIRM domain plays a role in tethering the HAT module to the remainder of SAGA. While recent cryo-EM studies have resolved the structure of the core of the SAGA complex, the HAT module subunits and molecular details of its interactions with the SAGA core could not be resolved. Here we show that the SWIRM domain is required for incorporation of the HAT module into the yeast SAGA complex, but not the ADA complex, a distinct six-protein acetyltransferase complex that includes the SAGA HAT module proteins. In the isolated Gcn5/Ada2/Ada3 HAT module, deletion of the SWIRM domain modestly increased activity but had negligible effect on nucleosome binding. Loss of the HAT module due to deletion of the SWIRM domain decreases the H2B deubiquitinating activity of SAGA, indicating a role for the HAT module in regulating SAGA DUB module activity. A model of the HAT module created with Alphafold Multimer provides insights into the structural basis for our biochemical data, as well as prior deletion studies.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194929"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10226619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The moonlighting of RAD23 in DNA repair and protein degradation","authors":"Martin Grønbæk-Thygesen ,&nbsp;Caroline Kampmeyer ,&nbsp;Kay Hofmann ,&nbsp;Rasmus Hartmann-Petersen","doi":"10.1016/j.bbagrm.2023.194925","DOIUrl":"10.1016/j.bbagrm.2023.194925","url":null,"abstract":"<div><p>A moonlighting protein is one, which carries out multiple, often wholly unrelated, functions. The RAD23 protein is a fascinating example of this, where the same polypeptide and the embedded domains function independently in both nucleotide excision repair (NER) and protein degradation via the ubiquitin-proteasome system (UPS). Hence, through direct binding to the central NER component XPC, RAD23 stabilizes XPC and contributes to DNA damage recognition. Conversely, RAD23 also interacts directly with the 26S proteasome and ubiquitylated substrates to mediate proteasomal substrate recognition. In this function, RAD23 activates the proteolytic activity of the proteasome and engages specifically in well-characterized degradation pathways through direct interactions with E3 ubiquitin-protein ligases and other UPS components. Here, we summarize the past 40 years of research into the roles of RAD23 in NER and the UPS.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194925"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage","authors":"Xianyan Hu ,&nbsp;Rong Zou ,&nbsp;Zaihui Zhang ,&nbsp;Jia Ji ,&nbsp;Jiqiang Li ,&nbsp;Xin-Yu Huo ,&nbsp;Di Liu ,&nbsp;Man-Xi Ge ,&nbsp;Meng-Ke Cui ,&nbsp;Ming-Zhi Wu ,&nbsp;Zhao-Peng Li ,&nbsp;Qingchen Wang ,&nbsp;Xiaoli Zhang ,&nbsp;Zai-Rong Zhang","doi":"10.1016/j.bbagrm.2023.194937","DOIUrl":"10.1016/j.bbagrm.2023.194937","url":null,"abstract":"<div><p><span><span>The transcription factor nuclear factor erythroid 2<span> like 1 (NFE2L1 or NRF1) regulates constitutive and inducible expression of proteasome subunits and assembly chaperones. The precursor of </span></span>NRF1 is integrated into the endoplasmic reticulum (ER) and can be retrotranslocated from the ER to the cytosol where it is processed by ubiquitin-directed endoprotease DDI2. DDI2 cleaves and activates NRF1 only when NRF1 is highly polyubiquitinated. It remains unclear how retrotranslocated NRF1 is primed with large amount of ubiquitin and/or very long polyubiquitin chain for subsequent processing. Here, we report that E3 </span>ligase<span> UBE4A catalyzes ubiquitination of retrotranslocated NRF1 and promotes its cleavage. Depletion of UBE4A reduces the amount of ubiquitin modified on NRF1, shortens the average length of polyubiquitin chain, decreases NRF1 cleavage efficiency and causes accumulation of non-cleaved, inactivated NRF1. Expression of a UBE4A mutant lacking ligase activity impairs the cleavage, likely due to a dominant negative effect. UBE4A interacts with NRF1 and the recombinant UBE4A can promote ubiquitination of retrotranslocated NRF1 in vitro. In addition, knocking out UBE4A reduces transcription of proteasomal subunits in cells. Our results indicate that UBE4A primes NRF1 for DDI2-mediated activation to facilitate expression of proteasomal genes.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194937"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}