{"id":"https://openalex.org/W2805630110","doi":null,"title":"Making sense from nonsense and missense : pharmacological rescue of mutant tumor suppressor p53","display_name":"Making sense from nonsense and missense : pharmacological rescue of mutant tumor suppressor p53","publication_year":2018,"publication_date":"2018-05-30","ids":{"openalex":"https://openalex.org/W2805630110","mag":"2805630110"},"language":"en","primary_location":{"id":"pmh:oai:figshare.com:article/26901940","doi":null,"is_oa":false,"landing_page_url":"https://figshare.com/articles/thesis/Making_sense_from_nonsense_and_missense_pharmacological_rescue_of_mutant_tumor_suppressor_p53/26901940","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://hdl.handle.net/10616/46364","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5011984735","display_name":"Meiqiongzi Zhang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Meiqiongzi Zhang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5011984735"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9961000084877014,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11884","display_name":"Redox biology and oxidative stress","score":0.0017000000225380063,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10294","display_name":"Cell death mechanisms and regulation","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tp53","display_name":"TP53","score":0.7490000128746033},{"id":"https://openalex.org/keywords/nonsense-mutation","display_name":"nonsense mutation","score":0.8759999871253967},{"id":"https://openalex.org/keywords/missense-mutations","display_name":"missense mutations","score":0.9940000176429749},{"id":"https://openalex.org/keywords/apr-246","display_name":"APR-246","score":0.9470000267028809},{"id":"https://openalex.org/keywords/prima-1met","display_name":"PRIMA-1MET","score":0.9850000143051147},{"id":"https://openalex.org/keywords/txnrd1","display_name":"thioredoxin reductase 1","score":0.6990000009536743},{"id":"https://openalex.org/keywords/redox-regulation","display_name":"redox regulation","score":0.4580000042915344},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.777999997138977},{"id":"https://openalex.org/keywords/aminoglycosides","display_name":"aminoglycosides","score":0.9049999713897705},{"id":"https://openalex.org/keywords/translational-readthrough","display_name":"translational readthrough","score":0.9620000123977661},{"id":"https://openalex.org/keywords/mdm2-inhibitors","display_name":"MDM2 inhibitors","score":0.7749999761581421},{"id":"https://openalex.org/keywords/nutlin","display_name":"nutlin","score":0.9929999709129333},{"id":"https://openalex.org/keywords/5-fluorouracil","display_name":"5-fluorouracil","score":0.9599999785423279},{"id":"https://openalex.org/keywords/p53-reactivation","display_name":"p53 reactivation","score":0.5239999890327454},{"id":"https://openalex.org/keywords/anticancer-drug-repurposing","display_name":"anticancer drug repurposing","score":0.699999988079071}],"concepts":[{"id":"https://openalex.org/C62923972","wikidata":"https://www.wikidata.org/wiki/Q600499","display_name":"Nonsense","level":3,"score":0.9248535633087158},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.6681126356124878},{"id":"https://openalex.org/C179185449","wikidata":"https://www.wikidata.org/wiki/Q219699","display_name":"Suppressor","level":3,"score":0.6505782604217529},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.6334478855133057},{"id":"https://openalex.org/C143141573","wikidata":"https://www.wikidata.org/wiki/Q7450971","display_name":"Sense (electronics)","level":2,"score":0.4757368564605713},{"id":"https://openalex.org/C96777560","wikidata":"https://www.wikidata.org/wiki/Q518638","display_name":"Nonsense mutation","level":5,"score":0.43306130170822144},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.37572863698005676},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.35698261857032776},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.29463857412338257},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.1909780502319336},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.18407270312309265},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.1569257378578186},{"id":"https://openalex.org/C147789679","wikidata":"https://www.wikidata.org/wiki/Q11372","display_name":"Physical chemistry","level":1,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"pmh:oai:figshare.com:article/26901940","doi":null,"is_oa":false,"landing_page_url":"https://figshare.com/articles/thesis/Making_sense_from_nonsense_and_missense_pharmacological_rescue_of_mutant_tumor_suppressor_p53/26901940","pdf_url":null,"source":{"id":"https://openalex.org/S4377196282","display_name":"Figshare","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I4210132348","host_organization_name":"Figshare (United Kingdom)","host_organization_lineage":["https://openalex.org/I4210132348"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},{"id":"pmh:oai:openarchive.ki.se:10616/46364","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/10616/46364","pdf_url":null,"source":{"id":"https://openalex.org/S4306400147","display_name":"Open Archive (Karolinska Institutet)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I28166907","host_organization_name":"Karolinska Institutet","host_organization_lineage":["https://openalex.org/I28166907"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralThesis"},{"id":"mag:2805630110","doi":null,"is_oa":false,"landing_page_url":"https://openarchive.ki.se/xmlui/handle/10616/46364","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:openarchive.ki.se:10616/46364","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/10616/46364","pdf_url":null,"source":{"id":"https://openalex.org/S4306400147","display_name":"Open Archive (Karolinska Institutet)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I28166907","host_organization_name":"Karolinska Institutet","host_organization_lineage":["https://openalex.org/I28166907"],"host_organization_lineage_names":[],"type":"repository"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"info:eu-repo/semantics/doctoralThesis"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":79,"referenced_works":["https://openalex.org/W70621156","https://openalex.org/W110290751","https://openalex.org/W129982716","https://openalex.org/W134485649","https://openalex.org/W167951030","https://openalex.org/W170595835","https://openalex.org/W613972939","https://openalex.org/W626649172","https://openalex.org/W1686601736","https://openalex.org/W1820845817","https://openalex.org/W1966163762","https://openalex.org/W1969524738","https://openalex.org/W1978406914","https://openalex.org/W1987584071","https://openalex.org/W1992685513","https://openalex.org/W1995768712","https://openalex.org/W1995925361","https://openalex.org/W1996649572","https://openalex.org/W2006422601","https://openalex.org/W2011096245","https://openalex.org/W2011452661","https://openalex.org/W2013493332","https://openalex.org/W2018385269","https://openalex.org/W2028166203","https://openalex.org/W2028387032","https://openalex.org/W2028553570","https://openalex.org/W2057775693","https://openalex.org/W2059971436","https://openalex.org/W2066841033","https://openalex.org/W2072319696","https://openalex.org/W2072590456","https://openalex.org/W2074545297","https://openalex.org/W2074785680","https://openalex.org/W2076732344","https://openalex.org/W2077168519","https://openalex.org/W2080125477","https://openalex.org/W2081465242","https://openalex.org/W2092560324","https://openalex.org/W2092902276","https://openalex.org/W2093221820","https://openalex.org/W2093863893","https://openalex.org/W2097616194","https://openalex.org/W2100252315","https://openalex.org/W2106787323","https://openalex.org/W2108966286","https://openalex.org/W2114843025","https://openalex.org/W2116156843","https://openalex.org/W2117450989","https://openalex.org/W2117617781","https://openalex.org/W2117692326","https://openalex.org/W2127692046","https://openalex.org/W2142461351","https://openalex.org/W2142723443","https://openalex.org/W2142765738","https://openalex.org/W2143554850","https://openalex.org/W2146546967","https://openalex.org/W2149441684","https://openalex.org/W2154171668","https://openalex.org/W2155570392","https://openalex.org/W2159334325","https://openalex.org/W2160345685","https://openalex.org/W2170147411","https://openalex.org/W2172183886","https://openalex.org/W2204583106","https://openalex.org/W2276371085","https://openalex.org/W2355389606","https://openalex.org/W2402691501","https://openalex.org/W2407075270","https://openalex.org/W2530014580","https://openalex.org/W2533733680","https://openalex.org/W2585983133","https://openalex.org/W2595234941","https://openalex.org/W2615677334","https://openalex.org/W2736528197","https://openalex.org/W2765939742","https://openalex.org/W2796592069","https://openalex.org/W2951449583","https://openalex.org/W4248748009","https://openalex.org/W7095779489"],"related_works":["https://openalex.org/W2276371085","https://openalex.org/W2064508063","https://openalex.org/W2803246487","https://openalex.org/W2951449583","https://openalex.org/W1980588579","https://openalex.org/W1711549046","https://openalex.org/W3127786418","https://openalex.org/W2980083275","https://openalex.org/W2225251024","https://openalex.org/W2558157752"],"abstract_inverted_index":{"A":[0],"large":[1],"fraction":[2],"of":[3,17,33,41,117,134,138,190,202,233,239,260,331,349,412,419,443,486,498,556,588,617,624],"human":[4,593],"tumors":[5,490],"carry":[6],"inactivating":[7],"mutations":[8,19,22],"in":[9,47,54,65,88,112,132,142,156,162,180,194,199,266,312,371,422,446,476,592],"the":[10,145,177,181,187,231,296,383,393,410,459,477,484,526],"TP53":[11,29,242,270],"tumor":[12,38,48,52,140,267,375,447,559,594],"suppressor":[13,560],"gene.":[14],"Approximately":[15],"75%":[16],"these":[18],"are":[20,26],"missense":[21,384,492],"and":[23,36,105,124,136,185,196,219,243,251,263,301,346,391,417,433,467,516,524,551,567,584,610],"around":[24],"10%":[25],"nonsense":[27,240,271,289,313,372,426,450,471,494,557,589,625],"mutations.":[28],"inactivation":[30],"allows":[31],"evasion":[32],"cell":[34,220,465],"death":[35,221,466],"rapid":[37],"progression.":[39],"Restoration":[40],"wild":[42,121],"type":[43,122],"p53":[44,58,69,119,203,262,264,310,319,333,369,421,445,561,591],"protein":[45,311,320,370],"expression":[46,416,442],"cells":[49,200,268,424,448,595],"can":[50,257,440],"suppress":[51],"growth":[53,141],"vivo.":[55],"Missense":[56],"mutant":[57,68,118,129,241,290,314,373,385,427,451,472,495,558,590,626],"is":[59,70,81,96,148,153,324],"often":[60],"expressed":[61],"at":[62],"high":[63],"levels":[64,259],"tumors.":[66],"Therefore,":[67],"a":[71,82,102,157,529],"promising":[72],"target":[73,288,334],"for":[74,470,489,615],"novel":[75,435,487,618],"targeted":[76],"cancer":[77,292,316,423,464,474],"therapy.":[78],"APR-246":[79,95,152,388,462],"(PRIMA-1Met)":[80],"low":[83],"molecular":[84],"compound":[85,387],"previously":[86],"discovered":[87],"our":[89,379],"group.":[90],"We":[91,399],"have":[92,229,280,400],"shown":[93,245,306,362,402],"that":[94,172,246,382,403,439,620],"converted":[97],"to":[98,110,120,128,211,216,235,287,307,366,395,414,528],"methylene":[99],"quinuclidinone":[100],"(MQ),":[101],"potent":[103],"electrophile":[104],"Michael":[106],"acceptor,":[107],"binding":[108],"covalently":[109],"cysteines":[111],"p53.":[113],"MQ":[114],"promotes":[115],"refolding":[116],"conformation":[123],"restores":[125],"normal":[126],"function":[127,418],"p53,":[130],"resulting":[131],"induction":[133],"apoptosis":[135],"inhibition":[137],"xenograft":[139],"mice.":[143],"However,":[144],"underlying":[146,461],"mechanism":[147,460],"not":[149],"fully":[150],"elucidated.":[151],"currently":[154],"tested":[155],"phase":[158],"II":[159],"clinical":[160],"trial":[161],"high-grade":[163],"serous":[164],"ovarian":[165],"cancer.":[166],"In":[167,225,273,336,377],"paper":[168,226,274,337],"I,":[169],"we":[170,228,276,339,430],"show":[171],"APR-246,":[173],"via":[174],"MQ,":[175],"targets":[176],"Sec":[178],"residue":[179],"redox":[182],"enzyme":[183,394,527],"TrxR1":[184,193,198,207,390],"inhibits":[186,389,520],"reducing":[188],"activity":[189,265],"both":[191],"recombinant":[192],"vitro":[195],"cellular":[197],"independently":[201],"status.":[204],"The":[205],"inhibited":[206],"maintains":[208],"its":[209],"ability":[210,232,286,411],"oxidase":[212],"NADPH,":[213],"which":[214],"contributes":[215],"oxidative":[217],"stress":[218],"induced":[222,321,463],"by":[223,322,329,363,562,596],"APR-246.":[224],"II,":[227],"confirmed":[230],"aminoglycosides":[234,250,413,566],"induce":[236,308,367,621],"translational":[237,622],"readthrough":[238,623],"also":[244,401],"combination":[247,404,563],"treatment":[248,405,488,564],"with":[249,284,406,425,449,565],"p53-Mdm2":[252,407],"inhibitors":[253,408],"such":[254],"as":[255,327,352,437],"nutlin":[256],"enhance":[258],"full-length":[261,309,368,420,444],"carrying":[269,491],"mutation.":[272],"III,":[275],"through":[277,599],"data":[278,600],"mining":[279],"identified":[281,340,431,598],"28":[282],"compounds":[283,304,355,360,436,438,597,619],"potential":[285],"TP53-carrying":[291,315,374],"cells.":[293,317,376],"Among":[294,357],"these,":[295,358],"known":[297],"anticancer":[298],"drug":[299],"5-FU":[300,323,432],"5":[302],"other":[303],"were":[305,361],"Full-length":[318],"transcriptionally":[325],"active":[326],"assessed":[328],"upregulation":[330],"several":[332,434],"genes.":[335],"IV,":[338],"65":[341],"compounds,":[342],"from":[343],"high-throughput":[344],"screening":[345,348,614],"FACS-based":[347],"chemical":[350],"libraries":[351],"candidate":[353],"readthrough-inducing":[354],"(CRICs).":[356],"7":[359],"Western":[364],"blotting":[365],"conclusion,":[378],"study":[380],"reveals":[381],"p53-reactivating":[386],"converts":[392,525],"an":[396],"NADPH":[397,531],"oxidase.":[398,532],"enhances":[409],"restore":[415],"TP53.":[428,452,496,627],"Furthermore,":[429],"rescue":[441,555],"Our":[453,479],"studies":[454],"shed":[455],"further":[456],"light":[457],"on":[458],"raise":[468],"possibilities":[469],"TP53-targeted":[473],"therapy":[475],"future.":[478],"results":[480],"may":[481],"ultimately":[482],"facilitate":[483],"development":[485],"or":[493],"List":[497],"scientific":[499],"papers":[500],"I.":[501],"Peng,":[502],"X.,":[503],"Zhang,":[504,541,576,604],"M.Q.,":[505],"Conserva,":[506],"F.,":[507],"Hosny,":[508],"G.,":[509,511],"Selivanova,":[510],"Bykov,":[512,549,582,608],"V.J.,":[513],"Arner,":[514],"E.S.,":[515],"Wiman,":[517,552,585,611],"K.G.":[518,553,586,612],"APR-246/PRIMA-1MET":[519],"thioredoxin":[521],"reductase":[522],"1":[523],"dedicated":[530],"Cell":[533],"Death":[534],"Dis.":[535],"(2013)":[536],"4,":[537],"e881.":[538],"https://doi.org/10.1038/cddis.2013.417":[539],"II.":[540],"M.,":[542,546,577,579,605],"Heldin,":[543,580,606],"A.,":[544,581,607],"Palomar-Siles,":[545,578],"Ohlin,":[547],"S.,":[548],"V.J.N.,":[550,583,609],"Synergistic":[554],"Mdm2":[568],"inhibitors.":[569],"Front":[570],"Oncol.":[571],"(2017)7,":[572],"323.":[573],"https://doi.org/10.3389/fonc.2017.00323":[574],"III.":[575],"Rescue":[587],"mining.":[601],"[Manuscript]":[602,628],"IV.":[603],"High-throughput":[613],"identification":[616]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2018-06-13T00:00:00"}