Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献_第9页

Protein post-translational modifications: A key factor in colorectal cancer resistance mechanisms 蛋白质翻译后修饰：结直肠癌癌症耐药机制的关键因素

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-08-23 DOI: 10.1016/j.bbagrm.2023.194977

Bo Bi , Miaojuan Qiu , Peng Liu , Qiang Wang , Yingfei Wen , You Li , Binbin Li , Yongshu Li , Yulong He , Jing Zhao

{"title":"Protein post-translational modifications: A key factor in colorectal cancer resistance mechanisms","authors":"Bo Bi , Miaojuan Qiu , Peng Liu , Qiang Wang , Yingfei Wen , You Li , Binbin Li , Yongshu Li , Yulong He , Jing Zhao","doi":"10.1016/j.bbagrm.2023.194977","DOIUrl":"10.1016/j.bbagrm.2023.194977","url":null,"abstract":"<div>Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Despite advances in treatment, drug resistance remains a critical impediment. Post-translational modifications (PTMs) regulate protein stability, localization, and activity, impacting vital cellular processes. Recent research has highlighted the essential role of PTMs in the development of CRC resistance. This review summarizes recent advancements in understanding PTMs' roles in CRC resistance, focusing on the latest discoveries. We discuss the functional impact of PTMs on signaling pathways and molecules involved in CRC resistance, progress in drug development, and potential therapeutic targets. We also summarize the primary enrichment methods for PTMs. Finally, we discuss current challenges and future directions, including the need for more comprehensive PTM analysis methods and PTM-targeted therapies. This review identifies potential therapeutic interventions for addressing medication resistance in CRC, proposes prospective therapeutic options, and gives an overview of the function of PTMs in CRC resistance.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194977"},"PeriodicalIF":4.7,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10494009","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}

引用次数: 0

Post-translational modifications of lysine-specific demethylase 1 赖氨酸特异性去甲基酶1的翻译后修饰

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-08-10 DOI: 10.1016/j.bbagrm.2023.194968

Dongha Kim , Hye Jin Nam , Sung Hee Baek

引用次数: 0

N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential 肾脏疾病中N6-甲基腺苷（m6A）甲基化的机制和治疗潜力

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-08-06 DOI: 10.1016/j.bbagrm.2023.194967

Yuting Sun , De Jin , Ziwei Zhang , Hangyu Ji , Xuedong An , Yuehong Zhang , Cunqing Yang , Wenjie Sun , Yuqing Zhang , Yingying Duan , Xiaomin Kang , Linlin Jiang , Xuefei Zhao , Fengmei Lian

{"title":"N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential","authors":"Yuting Sun , De Jin , Ziwei Zhang , Hangyu Ji , Xuedong An , Yuehong Zhang , Cunqing Yang , Wenjie Sun , Yuqing Zhang , Yingying Duan , Xiaomin Kang , Linlin Jiang , Xuefei Zhao , Fengmei Lian","doi":"10.1016/j.bbagrm.2023.194967","DOIUrl":"10.1016/j.bbagrm.2023.194967","url":null,"abstract":"<div>The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as “writers,” and demethylases, known as “erasers,” leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various diseases. Both physiologically and pathologically, m6A methylation plays a critical role in the initiation and progression of kidney disease. The methylation of m6A may also facilitate the early diagnosis and treatment of kidney diseases, according to accumulating research. This review aims to provide a comprehensive overview of the potential role and mechanism of m6A methylation in kidney diseases, as well as its potential application in the treatment of such diseases. There will be a thorough examination of m6A methylation mechanisms, paying particular attention to the interplay between m6A writers, m6A erasers, and m6A readers. Furthermore, this paper will elucidate the interplay between various kidney diseases and m6A methylation, summarize the expression patterns of m6A in pathological kidney tissues, and discuss the potential therapeutic benefits of targeting m6A in the context of kidney diseases.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194967"},"PeriodicalIF":4.7,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9993758","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}

引用次数: 0

ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway ETS2过表达通过ETS2/miR-155/STAT1/DNMT1反馈回路通路改善骨关节炎软骨损伤

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-07-30 DOI: 10.1016/j.bbagrm.2023.194965

Shuxiang Chen , Xiaotong Zhu , Wenhuan Ou , Le Kang , Jian Situ , Zhipeng Liao , Li Huang , Weizhong Qi , Songjia Ni

{"title":"ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway","authors":"Shuxiang Chen , Xiaotong Zhu , Wenhuan Ou , Le Kang , Jian Situ , Zhipeng Liao , Li Huang , Weizhong Qi , Songjia Ni","doi":"10.1016/j.bbagrm.2023.194965","DOIUrl":"10.1016/j.bbagrm.2023.194965","url":null,"abstract":"<div>Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development of osteoarthritis (OA), but the potential functions and mechanism of most transcription factors in OA has not been completely illuminated. In this study, we identified that transcription factor V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) was significantly down-regulated in OA cartilage and IL-1β-induced OA chondrocytes. Functional experiments in vitro demonstrated that the overexpressed ETS2 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and ECM degradation in IL-1β-induced OA chondrocytes, whereas the knockdown of ETS2 led to the opposite effects. Further in vivo studies have shown that up-regulated ETS2 dramatically ameliorates cartilage injury in DMM-induced OA mice. Mechanical studies have disclosed that DNMT1-mediated downregulation of ETS2 dramatically promotes STAT1 by inhibiting miR-155 transcription, and increased STAT1 initiates a feedback loop that may enhance DNMT1-mediated hypermethylation of ETS2 to inhibit ETS2 expression, thus forming a DNMT1/ETS2/miR-155/STAT1 feedback loop that inhibits MAPK signaling pathways and aggravates OA cartilage injury. In all, our results revealed that overexpression of ETS2 markedly ameliorated OA cartilage injury through the ETS2/miR-155/STAT1/DNMT1 feedback loop, providing a new perspective on the pathogenesis and therapeutic strategies for OA.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194965"},"PeriodicalIF":4.7,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10386661","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}

引用次数: 0

Multimerization of HIF enhances transcription of target genes containing the hypoxia ancillary sequence HIF的多聚增强了含有缺氧辅助序列的靶基因的转录

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-07-25 DOI: 10.1016/j.bbagrm.2023.194963

Tamara Rosell-Garcia , Sergio Rivas-Muñoz , Koryu Kin , Verónica Romero-Albillo , Silvia Alcaraz , Carlos Fernandez-Tornero , Fernando Rodriguez-Pascual

{"title":"Multimerization of HIF enhances transcription of target genes containing the hypoxia ancillary sequence","authors":"Tamara Rosell-Garcia , Sergio Rivas-Muñoz , Koryu Kin , Verónica Romero-Albillo , Silvia Alcaraz , Carlos Fernandez-Tornero , Fernando Rodriguez-Pascual","doi":"10.1016/j.bbagrm.2023.194963","DOIUrl":"10.1016/j.bbagrm.2023.194963","url":null,"abstract":"<div>Transcriptional activity of the hypoxia inducible factor (HIF) relies on the formation of a heterodimer composed of an oxygen-regulated α-subunit and a stably expressed β-subunit. Heterodimeric HIF activates expression by binding to RCGTG motifs within promoters of hypoxia-activated genes. Some hypoxia targets also possess an adjacent HIF ancillary sequence (HAS) reported to increase transcription but whose function remains obscure. Here, we investigate the contribution of the HAS element to the hypoxia response and its mechanism of action, using the HAS-containing prolyl 4-hydroxylase subunit α1 (P4HA1) as a gene model in NIH/3T3 mouse embryonic fibroblasts and HEK293 human embryonic kidney cells. Our HIF overexpression experiments demonstrate that the HAS motif is essential for full induction by hypoxia and that the presence of the tandem HAS/HIF, as opposed to HIF-only sequences, provides HIF proteins with the capacity to form complexes of stoichiometry beyond the classical heterodimer, likely tetramers, to cooperatively potentiate hypoxia-induced transcription. We also provide evidence of the crucial role played by the Fα helix of the PAS-B domain of the HIF1β subunit to support the interaction between heterodimers. Functional analysis showed that human genes containing the HAS/HIF motifs are better responders to hypoxia, and their promoters are enriched for specific transcription factor binding sites. Gene ontology enrichment revealed a predominance of HAS/HIF in genes primarily related to tissue formation and development. Our findings add an extra level of regulation of the hypoxia/HIF signaling through multimerization of HIF proteins on regulatory elements containing the HAS/HIF motifs.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194963"},"PeriodicalIF":4.7,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135904","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}

引用次数: 0

Damaged collagen detected by collagen hybridizing peptide as efficient diagnosis marker for early hepatic fibrosis 胶原杂交肽检测损伤胶原作为早期肝纤维化的有效诊断指标

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-06-01 DOI: 10.1016/j.bbagrm.2023.194928

Ping Tao , Jinfang Liu , Yuan Li , Tao Zhang , Fangzhou Wang , Lei Chang , Chonghui Li , Xinlan Ge , Tao Zuo , Shichun Lu , Yuanyuan Ruan , Zhimin Yang , Ping Xu

{"title":"Damaged collagen detected by collagen hybridizing peptide as efficient diagnosis marker for early hepatic fibrosis","authors":"Ping Tao , Jinfang Liu , Yuan Li , Tao Zhang , Fangzhou Wang , Lei Chang , Chonghui Li , Xinlan Ge , Tao Zuo , Shichun Lu , Yuanyuan Ruan , Zhimin Yang , Ping Xu","doi":"10.1016/j.bbagrm.2023.194928","DOIUrl":"10.1016/j.bbagrm.2023.194928","url":null,"abstract":"<div>Liver fibrosis is characterized by excessive synthesis and deposition of extracellular matrix (ECM) in liver tissues. However, it still has been lacking of early detection and diagnosis methods. The collagen hybridizing peptide (CHP) is a novel synthetic peptide that enables detection of collagen damage and tissue remodeling. Here, we showed that obvious CHP-positive staining could be detected in the liver while given CCl4 for only 3 days, which was significantly enhanced while given CCl4 for 7 days. However, H&E staining showed no significant changes in fibrous tissue, and sirius red-positive staining could only be observed while given CCl4 for 14 days. Moreover, CHP-positive staining enhanced initially at portal area which further extended into the hepatic lobule, which was increased more significantly than sirius red-positive staining in the model of 10 and 14 days. Further proteomic analysis of CHP-positive staining revealed that pathways associated with ECM remodeling were significantly increased, while retinol metabolism was downregulated. Meanwhile, proteins enriched in cellular gene transcription and signal transduction involved in fibrogenesis were also upregulated, suggesting that fibrosis occurred in CHP-positive staining. Our study provided evidence that CHP could detect the collagen damage in liver, which might be an efficient indicator for the diagnosis of liver fibrosis at a very early stage.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194928"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536210","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}

引用次数: 1

METTL3 activates PERK-eIF2α dependent coelomocyte apoptosis by targeting the endoplasmic reticulum degradation-related protein SEL1L in echinoderms METTL3通过靶向内质网降解相关蛋白SEL1L激活棘皮动物PERK-eIF2α依赖性腔胚细胞凋亡

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-06-01 DOI: 10.1016/j.bbagrm.2023.194927

Dongdong Li , Ming Guo , Zhimeng Lv , Yina Shao , Weikang Liang , Chenghua Li

{"title":"METTL3 activates PERK-eIF2α dependent coelomocyte apoptosis by targeting the endoplasmic reticulum degradation-related protein SEL1L in echinoderms","authors":"Dongdong Li , Ming Guo , Zhimeng Lv , Yina Shao , Weikang Liang , Chenghua Li","doi":"10.1016/j.bbagrm.2023.194927","DOIUrl":"10.1016/j.bbagrm.2023.194927","url":null,"abstract":"<div>N6-methyladenosine (m6A) plays an important role in regulating many physiological and disease processes in vertebrates, in which methyltransferase-like 3 (METTL3) is the best-known m6A methyltransferase. However, the functional roles of invertebrate METTL3 have not yet been highlighted. In this study, we found that METTL3 from Apostichopus japonicus (AjMETTL3) was significantly induced in coelomocytes accompanied by higher levels of m6A modification in response to Vibrio splendidus challenge. Overexpression or silencing of AjMETTL3 in coelomocytes increased or decreased the m6A levels and promoted or inhibited V. splendidus-induced coelomocyte apoptosis, respectively. To further explore the molecular mechanism of AjMETTL3-mediated coelomic immunity, m6A-seq analysis revealed that the endoplasmic reticulum-related degradation (ERAD) pathway was significantly enriched, in which suppressor/enhancer of Lin-12-like (AjSEL1L) was suggested to be a target of AjMETTL3 in a negative regulatory manner. Functional analysis revealed that the increased AjMETTL3 reduced the stability of AjSEL1L mRNA by targeting the m6A modification site of 2004 bp-GGACA-2008 bp. The decreased AjSEL1L was further confirmed to be involved in AjMETTL3-mediated coelomocyte apoptosis. Mechanistically, the inhibited AjSEL1L increased the transcription of AjOS9 and Ajp97 in the EARD pathway to promote ubiquitin protein accumulation and ER stress, which further activated AjPERK-AjeIF2α pathway dependent coelomocyte apoptosis, but not the AjIRE1 or AjATF6 pathway. Taken together, our results supported invertebrate METTL3-mediated coelomocyte apoptosis by regulating the PERK-eIF2α pathway.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194927"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543957","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}

引用次数: 0

Formation of aggresomes with hydrogel-like characteristics by proteasome inhibition 通过蛋白酶体抑制形成具有水凝胶特征的聚合体

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-06-01 DOI: 10.1016/j.bbagrm.2023.194932

Seo Hyeong Park , Sang-Eun Lee , Jun Hyoung Jeon , Jung Hoon Lee , Eisuke Itakura , Sunghoe Chang , Won Hoon Choi , Min Jae Lee

{"title":"Formation of aggresomes with hydrogel-like characteristics by proteasome inhibition","authors":"Seo Hyeong Park , Sang-Eun Lee , Jun Hyoung Jeon , Jung Hoon Lee , Eisuke Itakura , Sunghoe Chang , Won Hoon Choi , Min Jae Lee","doi":"10.1016/j.bbagrm.2023.194932","DOIUrl":"10.1016/j.bbagrm.2023.194932","url":null,"abstract":"<div>The spatiotemporal sequestration of misfolded proteins is a mechanism by which cells counterbalance proteome homeostasis upon exposure to various stress stimuli. Chronic inhibition of proteasomes results in a large, juxtanuclear, membrane-less inclusion, known as the aggresome. Although the molecular mechanisms driving its formation, clearance, and pathophysiological implications are continuously being uncovered, the biophysical aspects of aggresomes remain largely uncharacterized. Using fluorescence recovery after photobleaching and liquid droplet disruption assays, we found that the aggresomes are a homogeneously blended condensates with liquid-like properties similar to droplets formed via liquid–liquid phase separation. However, unlike fluidic liquid droplets, aggresomes have more viscosity and hydrogel-like characteristics. We also observed that the inhibition of aggresome formation using microtubule-disrupting agents resulted in less soluble and smaller cytoplasmic speckles, which was associated with marked cytotoxicity. Therefore, the aggresome appears to be cytoprotective and serves as a temporal reservoir for dysfunctional proteasomes and substrates that need to be degraded. Our results suggest that the aggresome assembles through distinct and potentially sequential processes of energy-dependent retrograde transportation and spontaneous condensation into a hydrogel.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194932"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914451","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}

引用次数: 2

Iron restriction increases the expression of a cytotoxic cysteine proteinase TvCP2 by a novel mechanism of tvcp2 mRNA alternative polyadenylation in Trichomonas vaginalis 铁限制通过阴道毛滴虫TvCP2 mRNA选择性聚腺苷化的新机制增加了细胞毒性半胱氨酸蛋白酶TvCP2的表达

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-06-01 DOI: 10.1016/j.bbagrm.2023.194935

Luis Alberto Rivera-Rivas, Rossana Arroyo

{"title":"Iron restriction increases the expression of a cytotoxic cysteine proteinase TvCP2 by a novel mechanism of tvcp2 mRNA alternative polyadenylation in Trichomonas vaginalis","authors":"Luis Alberto Rivera-Rivas, Rossana Arroyo","doi":"10.1016/j.bbagrm.2023.194935","DOIUrl":"10.1016/j.bbagrm.2023.194935","url":null,"abstract":"<div>Trichomonas vaginalis TvCP2 (TVAG_057000) is a cytotoxic cysteine proteinase (CP) expressed under iron-limited conditions. This work aimed to identify one of the mechanisms of tvcp2 gene expression regulation by iron at the posttranscriptional level. We checked tvcp2 mRNA stability under both iron-restricted (IR) and high iron (HI) conditions in the presence of actinomycin D. Greater stability of the tvcp2 mRNA under the IR than in HI conditions was observed, as expected. In silico analysis of the 3′ regulatory region showed the presence of two putative polyadenylation signals in the tvcp2 transcript. By 3′-RACE assays, we demonstrated the existence of two isoforms of the tvcp2 mRNA with different 3′-UTR that resulted in more TvCP2 protein under IR than in HI conditions detected by WB assays. Additionally, we searched for homologs of the trichomonad polyadenylation machinery by an in silico analysis in the genome database, TrichDB. 16 genes that encode proteins that could be part of the trichomonad polyadenylation machinery were found. qRT-PCR assays showed that most of these genes were positively regulated by iron. Thus, our results show the presence of alternative polyadenylation as a novel iron posttranscriptional regulatory mechanism in T. vaginalis for the tvcp2 gene expression.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194935"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914455","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}

引用次数: 0

The N-degron pathway: From basic science to therapeutic applications N-degron通路:从基础科学到治疗应用

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-06-01 DOI: 10.1016/j.bbagrm.2023.194934

Ah Jung Heo , Su Bin Kim , Yong Tae Kwon , Chang Hoon Ji

{"title":"The N-degron pathway: From basic science to therapeutic applications","authors":"Ah Jung Heo , Su Bin Kim , Yong Tae Kwon , Chang Hoon Ji","doi":"10.1016/j.bbagrm.2023.194934","DOIUrl":"10.1016/j.bbagrm.2023.194934","url":null,"abstract":"<div>The N-degron pathway is a degradative system in which single N-terminal (Nt) amino acids regulate the half-lives of proteins and other biological materials. These determinants, called N-degrons, are recognized by N-recognins that link them to the ubiquitin (Ub)-proteasome system (UPS) or autophagy-lysosome system (ALS). In the UPS, the Arg/N-degron pathway targets the Nt-arginine (Nt-Arg) and other N-degrons to assemble Lys48 (K48)-linked Ub chains by UBR box N-recognins for proteasomal proteolysis. In the ALS, Arg/N-degrons are recognized by the N-recognin p62/SQSTSM-1/Sequestosome-1 to induce cis-degradation of substrates and trans-degradation of various cargoes such as protein aggregates and subcellular organelles. This crosstalk between the UPS and ALP involves reprogramming of the Ub code. Eukaryotic cells developed diverse ways to target all 20 principal amino acids for degradation. Here we discuss the components, regulation, and functions of the N-degron pathways, with an emphasis on the basic mechanisms and therapeutic applications of Arg/N-degrons and N-recognins.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194934"},"PeriodicalIF":4.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9536217","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}

引用次数: 1