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The ubiquitin codes in cellular stress responses

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Protein & Cell 2024年第3期15卷 157-190页

作者： Xiangpeng Sheng Zhixiong Xia Hanting Yang Ronggui Hu Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key Laboratory of molecular biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China State Key Laboratory of Animal Disease Control Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China department of Neurology State Key Laboratory of Medical NeurobiologyInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceZhongshan HospitalFudan UniversityShanghai 200032China

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in *** evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional *** forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress *** ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed *** this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin *** review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

关键词： ubiquitin E3 ligase environmental stresses intercellular stresses stress response homeostasis

Suffocated shoots:Hypoxia-induced synthesis of salicylic acid inhibits plant regeneration

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molecular Plant 2024年第4期17卷 528-530页

作者： Ximena Chirinos Francesco Licausi department of biology University of OxfordSouth Parks RoadOxford OX13RBUK

Plant cells possess the unique ability to revert differentiated somatic cells back to a pluripotent state,a trait utilized in in vitro tissue *** plant propagation strategy involves the exogenous supplementation of auxin and cytokinin,two phytohormones that promote cellular reprogramming and de novo *** exposed to an auxin-rich medium,somatic cells proliferate and form the callus,a pluripotent cell *** the attainment of pluripotency,the callus can be transferred to a cytokinin-rich medium to induce shoot regeneration.

关键词： plant synthesis transferred

Emerging role of cellular senescence in normal lung development and perinatal lung injury

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 10-16页

作者： Phyllis A.Dennery Hongwei Yao department of molecular biology Cell Biology&BiochemistryDivision of Biology and MedicineBrown UniversityProvidenceRI 02912USA department of Pediatrics Warren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external *** cells are typically enlarged and flattened,and characterized by numerous molecular *** latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory *** features vary depending on the stressor leading to senescence and the type of *** senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related ***,senescence can also both promote and inhibit wound healing *** recently report that senescence as a programmed pro-cess contributes to normal lung *** senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this ***,this senescence results in neonatal lung *** this review,we briefly discuss the molecular features of *** then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving ***,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关键词： Senescence Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics

Know Thy Enemy:Untangling the Mysteries of Neuropathic Pain

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Neuroscience Bulletin 2021年第11期37卷 1639-1641页

作者： Mahar Fatima Chia Chun Hor Bo Duan department of molecular Cellularand Developmental BiologyUniversity of MichiganAnn ArborMI48109USA

Acute pain plays an important physiological role as a warning system for the ***,in many patients,nerve danlage leads to neuropathic pain that can last for years and disrupts their quality of ***.

关键词： Acute pain patients

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

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Journal of molecular Cell biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante Manuela Zangrossi Elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin Filippo Torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli Sara N.Richter Marco Montagner Graziano Martello department of molecular Medicine University of PaduaPadua 35121Italy department of biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto Institute of Oncology IOV-IRCCS Padua 35128Italy department of Comparative Biomedicine and Food Science University of PaduaPadua 35020Italy Telethon Institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy Microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US Food and Drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals N-acetyl cysteine

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce department of Cancer biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA department of Clinical and molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

Recent advances to address challenges in extracellular vesicle-based applications for lung cancer

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3855-3875页

作者： Gaigai Huang Wenshu Zheng Yu Zhou Meihua Wan Tony Hu department of Clinical Laboratory the First People’s Hospital of Shuangliu District(West China Airport Hospital of Sichuan University)Chengdu 610200China Center for cellular and molecular Diagnostics Tulane University School of MedicineNew OrleansLA 70112USA department of Integrated Traditional Chinese and Western Medicine West China Hospital of Sichuan UniversityChengdu 610200China The First People’s Hospital of Shuangliu District(West China Airport Hospital of Sichuan University) Chengdu 610200China

Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic ***,extracellular vesicles(EVs),functioning as natural carriers for intercellular communication,have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes,including cytosolic proteins,cell surface proteins,microRNA,lncRNA,circRNA,DNA,and *** are increasingly recognized as a valuable resource for non-invasive liquid biopsy,as well as drug delivery platforms,and anticancer vaccines for precision medicine in lung ***,given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer,we discuss this topic from a translational *** delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.

关键词： Lung cancer Extracellular vesicles Therapy resistance Delivery Diagnostics Therapeutics Nanotechnology Engineering

MAX2 Affects Multiple Hormones to Promote Photomorphogenesis

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molecular Plant 2012年第3期5卷 750-762页

作者： Hui Shen Ling Zhu Qing-Yun Bu Enamul Huq Section of molecular Cell and developmental biology and the Institute for cellular and molecular biology University of Texas at Austin Austin TX 78712 USA

Ubiquitin-26S proteasome system （UPS） has been shown to play central roles in light and hormone-regulated plant growth and development. Previously, we have shown that MAX2, an F-box protein, positively regulates facets of photomorphogenic development in response to light. However, how MAX2 controls these responses is still unknown. Here, we show that MAX2 oppositely regulates GA and ABA biosynthesis to optimize seed germination in response to light. Dose-response curves showed that max2 seeds are hyposensitive to GA and hypersensitive to ABA in seed ger- mination responses. RT-PCR assays demonstrated that the expression of GA biosynthetic genes is down-regulated, while the expression of GA catabolic genes is up-regulated in the rnax2 seeds compared to wild-type. Interestingly, expression of both ABA biosynthetic and catabolic genes is up-regulated in the max2 seeds compared to wild-type. Treatment with an auxin transport inhibitor, NPA, showed that increased auxin transport in max2 seedlings contributes to the long hypocotyl phenotype under light. Moreover, light-signaling phenotypes are restricted to max2, as the biosynthetic mutants in the strigolactone pathway, max1, max3, and rnax4, did not display any defects in seed germination and seedling de-etiolation compared to wild-type. Taken together, these data suggest that MAX2 modulates multiple hormone pathways to affect photomorphogenesis.

关键词： Arabidopsis F-box protein photomorphogenesis protein degradation strigolactone SCF complex

Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

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Cancer Innovation 2024年第2期3卷 80-95页

作者： Satoru Sasagawa Jun Kumai Toru Wakamatsu Yoshihiro Yui molecular biology Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Sarcoma Treatment Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan department of Musculoskeletal Oncology Service Osaka International Cancer InstituteOsakaJapan

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the *** deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi *** provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture ***:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective ***38 was concomitantly used as an ameliorant drug with romidepsin ***,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug *** addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on ***:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell *** the apoptotic inducible cells,co-treatment with SN38 enhanced cell *** nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction *** a novel efficacy of SN38,we revealed TWIST1 suppression in SS *** the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive *** demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the ***:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and

关键词： HDAC inhibitor MICA/B SN38 spheroid synovial sarcoma TWIST1