{"id":"https://openalex.org/W2169504616","doi":null,"title":"Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis","display_name":"Inhibition of Deubiquitinase Activity and Ubiquitination of Jak2 Blocks Cytokine Signaling and Induces Tumor Cell Apoptosis","publication_year":2010,"publication_date":"2010-01-01","ids":{"openalex":"https://openalex.org/W2169504616","mag":"2169504616"},"language":"en","primary_location":{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1062","doi":null,"is_oa":false,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/42","pdf_url":null,"source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5000154659","display_name":"Vaibhav Kapuria","orcid":"https://orcid.org/0000-0003-1514-419X","observed_orcids":["https://orcid.org/0000-0003-1514-419X"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Vaibhav Kapuria","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5000154659"],"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/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9868000149726868,"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"}},"topics":[{"id":"https://openalex.org/T11041","display_name":"Ubiquitin and proteasome pathways","score":0.9868000149726868,"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/T11503","display_name":"Cytokine Signaling Pathways and Interactions","score":0.011699999682605267,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.0005000000237487257,"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/jak2","display_name":"JAK2","score":0.6589999794960022},{"id":"https://openalex.org/keywords/deubiquitinase-inhibition","display_name":"deubiquitinase inhibition","score":0.8169999718666077},{"id":"https://openalex.org/keywords/ubiquitination","display_name":"ubiquitination","score":0.8679999709129333},{"id":"https://openalex.org/keywords/jak-stat-signaling","display_name":"JAK/STAT signaling","score":0.734000027179718},{"id":"https://openalex.org/keywords/cytokine-signaling","display_name":"cytokine signaling","score":0.8659999966621399},{"id":"https://openalex.org/keywords/tumor-cell-apoptosis","display_name":"tumor cell apoptosis","score":0.8510000109672546},{"id":"https://openalex.org/keywords/wp1130","display_name":"WP1130","score":0.972000002861023},{"id":"https://openalex.org/keywords/aggresomes","display_name":"aggresomes","score":0.9390000104904175},{"id":"https://openalex.org/keywords/usp9x","display_name":"USP9X","score":0.8730000257492065},{"id":"https://openalex.org/keywords/usp5","display_name":"USP5","score":0.9729999899864197},{"id":"https://openalex.org/keywords/usp14","display_name":"USP14","score":1.0},{"id":"https://openalex.org/keywords/uch37","display_name":"UCH37","score":0.9990000128746033},{"id":"https://openalex.org/keywords/mcl-1","display_name":"Mcl-1","score":0.9539999961853027},{"id":"https://openalex.org/keywords/p53","display_name":"p53","score":0.9900000095367432},{"id":"https://openalex.org/keywords/anti-apoptotic-proteins","display_name":"anti-apoptotic proteins","score":0.6570000052452087}],"concepts":[{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.730075478553772},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.6303918361663818},{"id":"https://openalex.org/C182561583","wikidata":"https://www.wikidata.org/wiki/Q7876535","display_name":"Ubiquitin-conjugating enzyme","level":5,"score":0.518256664276123},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4878408908843994},{"id":"https://openalex.org/C157333092","wikidata":"https://www.wikidata.org/wiki/Q902835","display_name":"JAK-STAT signaling pathway","level":4,"score":0.4711766839027405},{"id":"https://openalex.org/C27740335","wikidata":"https://www.wikidata.org/wiki/Q14878333","display_name":"Proteasome","level":2,"score":0.44037359952926636},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4253881871700287},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4251420497894287},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.40582191944122314},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2517053782939911},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.18199166655540466},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.08038240671157837},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1062","doi":null,"is_oa":false,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/42","pdf_url":null,"source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},{"id":"mag:2169504616","doi":null,"is_oa":false,"landing_page_url":"http://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1062&context=utgsbs_dissertations","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":null,"sustainable_development_goals":[{"score":0.8048999905586243,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":195,"referenced_works":["https://openalex.org/W1225996684","https://openalex.org/W1245819034","https://openalex.org/W1505115118","https://openalex.org/W1544215724","https://openalex.org/W1548640328","https://openalex.org/W1549578642","https://openalex.org/W1553797204","https://openalex.org/W1640016724","https://openalex.org/W1656644461","https://openalex.org/W1831428880","https://openalex.org/W1954801073","https://openalex.org/W1964305312","https://openalex.org/W1967391569","https://openalex.org/W1968885796","https://openalex.org/W1970091268","https://openalex.org/W1970232220","https://openalex.org/W1972927903","https://openalex.org/W1975202136","https://openalex.org/W1975512656","https://openalex.org/W1978672439","https://openalex.org/W1980471295","https://openalex.org/W1980568348","https://openalex.org/W1980830373","https://openalex.org/W1981799488","https://openalex.org/W1984848300","https://openalex.org/W1985275612","https://openalex.org/W1986029666","https://openalex.org/W1987467454","https://openalex.org/W1987583882","https://openalex.org/W1988146888","https://openalex.org/W1988617344","https://openalex.org/W1991249033","https://openalex.org/W1991539695","https://openalex.org/W1991841644","https://openalex.org/W1993520606","https://openalex.org/W1994852323","https://openalex.org/W1995789798","https://openalex.org/W1995981641","https://openalex.org/W1996015633","https://openalex.org/W1997935194","https://openalex.org/W2000017794","https://openalex.org/W2001234769","https://openalex.org/W2002246876","https://openalex.org/W2002782759","https://openalex.org/W2003939839","https://openalex.org/W2004175299","https://openalex.org/W2005177899","https://openalex.org/W2005274511","https://openalex.org/W2006917576","https://openalex.org/W2008409819","https://openalex.org/W2011361940","https://openalex.org/W2012828222","https://openalex.org/W2013012256","https://openalex.org/W2013035261","https://openalex.org/W2013082795","https://openalex.org/W2013339424","https://openalex.org/W2014215007","https://openalex.org/W2016351010","https://openalex.org/W2017047552","https://openalex.org/W2020031294","https://openalex.org/W2022690300","https://openalex.org/W2022819740","https://openalex.org/W2023434020","https://openalex.org/W2024282024","https://openalex.org/W2024384866","https://openalex.org/W2024719523","https://openalex.org/W2025236720","https://openalex.org/W2026043555","https://openalex.org/W2027072436","https://openalex.org/W2027213843","https://openalex.org/W2027382240","https://openalex.org/W2028070445","https://openalex.org/W2028157992","https://openalex.org/W2028553570","https://openalex.org/W2032975232","https://openalex.org/W2033055043","https://openalex.org/W2033228162","https://openalex.org/W2034016996","https://openalex.org/W2034894297","https://openalex.org/W2035094622","https://openalex.org/W2036727875","https://openalex.org/W2036806530","https://openalex.org/W2037454778","https://openalex.org/W2039778506","https://openalex.org/W2040146122","https://openalex.org/W2040614735","https://openalex.org/W2042011247","https://openalex.org/W2042122259","https://openalex.org/W2042518552","https://openalex.org/W2042960115","https://openalex.org/W2043141000","https://openalex.org/W2043188148","https://openalex.org/W2045991166","https://openalex.org/W2049145190","https://openalex.org/W2049545543","https://openalex.org/W2049748848","https://openalex.org/W2051181798","https://openalex.org/W2051316659","https://openalex.org/W2051994734","https://openalex.org/W2055722788","https://openalex.org/W2057360098","https://openalex.org/W2058218787","https://openalex.org/W2059193889","https://openalex.org/W2060383679","https://openalex.org/W2060402899","https://openalex.org/W2060663461","https://openalex.org/W2060945380","https://openalex.org/W2065601509","https://openalex.org/W2067563932","https://openalex.org/W2067653691","https://openalex.org/W2068232821","https://openalex.org/W2068299688","https://openalex.org/W2068931555","https://openalex.org/W2069788390","https://openalex.org/W2069800916","https://openalex.org/W2071666904","https://openalex.org/W2074356752","https://openalex.org/W2075110858","https://openalex.org/W2076120507","https://openalex.org/W2077625855","https://openalex.org/W2078072437","https://openalex.org/W2080182587","https://openalex.org/W2081414779","https://openalex.org/W2083802827","https://openalex.org/W2085484189","https://openalex.org/W2087343043","https://openalex.org/W2087482176","https://openalex.org/W2088724822","https://openalex.org/W2090926709","https://openalex.org/W2094362595","https://openalex.org/W2098437309","https://openalex.org/W2098731025","https://openalex.org/W2099002508","https://openalex.org/W2099857411","https://openalex.org/W2100930825","https://openalex.org/W2101362932","https://openalex.org/W2103079856","https://openalex.org/W2104485296","https://openalex.org/W2105555634","https://openalex.org/W2106571571","https://openalex.org/W2108932391","https://openalex.org/W2110803617","https://openalex.org/W2111129974","https://openalex.org/W2114713566","https://openalex.org/W2114765412","https://openalex.org/W2117396050","https://openalex.org/W2118225942","https://openalex.org/W2118310862","https://openalex.org/W2118849870","https://openalex.org/W2119301405","https://openalex.org/W2119680582","https://openalex.org/W2123281631","https://openalex.org/W2124975942","https://openalex.org/W2125905711","https://openalex.org/W2127048642","https://openalex.org/W2130935241","https://openalex.org/W2131423447","https://openalex.org/W2131612416","https://openalex.org/W2134404356","https://openalex.org/W2134582745","https://openalex.org/W2134779016","https://openalex.org/W2136128861","https://openalex.org/W2138077682","https://openalex.org/W2138102966","https://openalex.org/W2139364069","https://openalex.org/W2139630089","https://openalex.org/W2139937771","https://openalex.org/W2141035944","https://openalex.org/W2144198294","https://openalex.org/W2144664431","https://openalex.org/W2145216906","https://openalex.org/W2145345398","https://openalex.org/W2147005308","https://openalex.org/W2149761960","https://openalex.org/W2150123812","https://openalex.org/W2150857908","https://openalex.org/W2151513527","https://openalex.org/W2151881294","https://openalex.org/W2155330223","https://openalex.org/W2155449991","https://openalex.org/W2158359547","https://openalex.org/W2158602749","https://openalex.org/W2160380481","https://openalex.org/W2164453525","https://openalex.org/W2164750828","https://openalex.org/W2165495560","https://openalex.org/W2166735794","https://openalex.org/W2166834621","https://openalex.org/W2166987747","https://openalex.org/W2168133067","https://openalex.org/W2169894449","https://openalex.org/W2175994433","https://openalex.org/W2303212700","https://openalex.org/W2329648702","https://openalex.org/W2579219442"],"related_works":["https://openalex.org/W2076884995","https://openalex.org/W2134404356","https://openalex.org/W2581984460","https://openalex.org/W2731696857","https://openalex.org/W2571467780","https://openalex.org/W2098437309","https://openalex.org/W3046261291","https://openalex.org/W2480986700","https://openalex.org/W2024146059","https://openalex.org/W4283310777"],"abstract_inverted_index":{"The":[0],"Jak-stat":[1],"pathway":[2],"is":[3,9],"critical":[4],"for":[5,58],"cellular":[6],"proliferation":[7],"and":[8,54,72,101,156,169,177],"commonly":[10],"found":[11],"to":[12,112],"be":[13],"deregulated":[14],"in":[15,165,193],"many":[16],"solid":[17],"tumors":[18],"as":[19,21,75,140,175,203],"well":[20],"hematological":[22],"malignancies.":[23],"Such":[24],"findings":[25],"have":[26],"spurred":[27],"the":[28,46,130,149,194],"development":[29],"of":[30,68,79,104,118,129,132,134,152,161,167,171,186,197],"novel":[31,199,212],"therapeutic":[32],"agents":[33],"that":[34,96,137,183],"specifically":[35,147],"inhibit":[36,89],"Jak2":[37,49,80,90,105,190],"kinase,":[38],"thereby":[39],"suppressing":[40,207],"tumor":[41],"cell":[42],"growth.":[43],"Tyrphostin":[44],"AG490,":[45,84],"first":[47],"described":[48,189],"inhibitor,":[50,206],"displays":[51],"poor":[52],"pharmacology":[53],"requires":[55],"high":[56],"concentrations":[57],"anti-tumor":[59],"activities.":[60],"Our":[61,93,180],"research":[62],"group":[63],"screened":[64],"a":[65,76,141,187,198,204,211],"small":[66],"library":[67],"AG490":[69],"structural":[70],"analogues":[71],"identified":[73],"WP1130":[74,85,97,114,135,138,158],"potent":[77],"inhibitor":[78,191],"signaling.":[81],"However,":[82],"unlike":[83],"did":[86],"not":[87],"directly":[88],"kinase":[91],"activity.":[92,126],"results":[94,181,192],"show":[95],"induces":[98,116],"rapid":[99],"ubiquitination":[100],"subsequent":[102],"re-localization":[103],"into":[106],"signaling":[107,209],"incompetent":[108],"aggresomes.":[109],"In":[110],"addition":[111],"Jak2,":[113],"also":[115],"accumulation":[117],"other":[119],"ubiquitinated":[120],"proteins":[121],"without":[122],"inhibiting":[123],"20S":[124],"proteasome":[125],"Further":[127],"analysis":[128],"mechanism":[131],"action":[133],"revealed":[136],"acts":[139,202],"partly":[142],"selective":[143],"DUB":[144,205],"inhibitor.":[145],"It":[146],"inhibits":[148],"deubiquitinase":[150],"activity":[151],"USP9x,":[153],"USP5,":[154],"USP14":[155],"UCH37.":[157],"mediated":[159],"inhibition":[160],"tumor-associated":[162],"DUBs":[163],"resulted":[164],"down-regulation":[166],"anti-apoptotic":[168],"up-regulation":[170],"pro-apoptotic":[172],"proteins,":[173],"such":[174],"MCL-1":[176],"p53":[178],"respectively.":[179],"demonstrate":[182],"chemical":[184],"modification":[185],"previously":[188],"unexpected":[195],"discovery":[196],"compound":[200],"which":[201],"Jak-Stat":[208],"by":[210],"mechanism.":[213]},"counts_by_year":[],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}
