{"id":"https://openalex.org/W1601950512","doi":null,"title":"Defining the Role of GGTase-I in the Development of Rheumatoid Arthritis and Atherosclerosis","display_name":"Defining the Role of GGTase-I in the Development of Rheumatoid Arthritis and Atherosclerosis","publication_year":2012,"publication_date":"2012-05-08","ids":{"openalex":"https://openalex.org/W1601950512","mag":"1601950512"},"language":"en","primary_location":{"id":"pmh:oai:gupea.ub.gu.se:2077/28962","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/2077/28962","pdf_url":"http://hdl.handle.net/2077/28962","source":{"id":"https://openalex.org/S4306401168","display_name":"Gothenburg University Publications Electronic Archive (Gothenburg University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I881427289","host_organization_name":"University of Gothenburg","host_organization_lineage":["https://openalex.org/I881427289"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Doctoral thesis"},"volume":null,"type":"dissertation","indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"http://hdl.handle.net/2077/28962","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5029722381","display_name":"Omar M. Khan","orcid":"https://orcid.org/0000-0001-7062-4677","observed_orcids":["https://orcid.org/0000-0001-7062-4677"]},"institutions":[{"id":"https://openalex.org/I881427289","display_name":"University of Gothenburg","ror":"https://ror.org/01tm6cn81","country_code":"SE","type":"education","lineage":["https://openalex.org/I881427289"]}],"countries":["SE"],"is_corresponding":true,"raw_author_name":"Omar M. Khan","raw_affiliation_strings":["University of Gothenburg"],"raw_orcid":"https://orcid.org/0000-0001-7062-4677","affiliations":[{"raw_affiliation_string":"University of Gothenburg","institution_ids":["https://openalex.org/I881427289"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5029722381"],"corresponding_institution_ids":["https://openalex.org/I881427289"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.6509000062942505,"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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.6509000062942505,"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/T10200","display_name":"Rheumatoid Arthritis Research and Therapies","score":0.3142000138759613,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"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/T12955","display_name":"Atherosclerosis and Cardiovascular Diseases","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"}}],"keywords":[{"id":"https://openalex.org/keywords/rheumatoid-arthritis","display_name":"rheumatoid arthritis","score":0.8769999742507935},{"id":"https://openalex.org/keywords/atherosclerosis","display_name":"atherosclerosis","score":0.9990000128746033},{"id":"https://openalex.org/keywords/rho-gtpases","display_name":"Rho GTPases","score":0.9179999828338623},{"id":"https://openalex.org/keywords/geranylgeranylation","display_name":"geranylgeranylation","score":0.9179999828338623},{"id":"https://openalex.org/keywords/macrophages","display_name":"macrophages","score":0.8700000047683716},{"id":"https://openalex.org/keywords/rac1","display_name":"Rac1","score":0.9200000166893005},{"id":"https://openalex.org/keywords/cdc42","display_name":"Cdc42","score":0.8870000243186951},{"id":"https://openalex.org/keywords/rhoa","display_name":"RhoA","score":0.9990000128746033},{"id":"https://openalex.org/keywords/p38-mapk","display_name":"p38 MAPK","score":0.8510000109672546},{"id":"https://openalex.org/keywords/nf-kappab","display_name":"NF-\u03baB","score":0.9959999918937683},{"id":"https://openalex.org/keywords/pro-inflammatory-cytokines","display_name":"inflammatory cytokines","score":0.9610000252723694},{"id":"https://openalex.org/keywords/foam-cell-formation","display_name":"foam cell formation","score":0.7329999804496765},{"id":"https://openalex.org/keywords/cholesterol-efflux","display_name":"cholesterol efflux","score":0.9710000157356262},{"id":"https://openalex.org/keywords/cyclooxygenase-2","display_name":"cyclooxygenase-2","score":0.7689999938011169},{"id":"https://openalex.org/keywords/ppargamma","display_name":"PPAR\u03b3","score":0.9940000176429749},{"id":"https://openalex.org/keywords/cd36","display_name":"CD36","score":0.8289999961853027},{"id":"https://openalex.org/keywords/ldl-receptor-deficient-mice","display_name":"LDL receptor-deficient mice","score":0.8169999718666077},{"id":"https://openalex.org/keywords/statins","display_name":"statins","score":0.42800000309944153}],"concepts":[{"id":"https://openalex.org/C2777575956","wikidata":"https://www.wikidata.org/wiki/Q187255","display_name":"Rheumatoid arthritis","level":2,"score":0.765343189239502},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4460149109363556},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4087134301662445}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:gupea.ub.gu.se:2077/28962","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/2077/28962","pdf_url":"http://hdl.handle.net/2077/28962","source":{"id":"https://openalex.org/S4306401168","display_name":"Gothenburg University Publications Electronic Archive (Gothenburg University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I881427289","host_organization_name":"University of Gothenburg","host_organization_lineage":["https://openalex.org/I881427289"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Doctoral thesis"},{"id":"mag:1601950512","doi":null,"is_oa":false,"landing_page_url":"https://gupea.ub.gu.se/bitstream/2077/28962/1/gupea_2077_28962_1.pdf","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:gupea.ub.gu.se:2077/28962","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/2077/28962","pdf_url":"http://hdl.handle.net/2077/28962","source":{"id":"https://openalex.org/S4306401168","display_name":"Gothenburg University Publications Electronic Archive (Gothenburg University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I881427289","host_organization_name":"University of Gothenburg","host_organization_lineage":["https://openalex.org/I881427289"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Doctoral thesis"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W1601950512.pdf","grobid_xml":"https://content.openalex.org/works/W1601950512.grobid-xml"},"referenced_works_count":241,"referenced_works":["https://openalex.org/W6497050","https://openalex.org/W18482866","https://openalex.org/W25794465","https://openalex.org/W38523360","https://openalex.org/W165352238","https://openalex.org/W200118474","https://openalex.org/W295940176","https://openalex.org/W1491433568","https://openalex.org/W1493676054","https://openalex.org/W1499516173","https://openalex.org/W1507719842","https://openalex.org/W1508576187","https://openalex.org/W1524121247","https://openalex.org/W1524478189","https://openalex.org/W1527774170","https://openalex.org/W1563425172","https://openalex.org/W1565110330","https://openalex.org/W1572797926","https://openalex.org/W1586099293","https://openalex.org/W1588094863","https://openalex.org/W1595757864","https://openalex.org/W1607399348","https://openalex.org/W1649367075","https://openalex.org/W1805968117","https://openalex.org/W1870088907","https://openalex.org/W1907316344","https://openalex.org/W1910518513","https://openalex.org/W1948530489","https://openalex.org/W1948985515","https://openalex.org/W1964286374","https://openalex.org/W1964551999","https://openalex.org/W1964667616","https://openalex.org/W1964816418","https://openalex.org/W1966848219","https://openalex.org/W1968171440","https://openalex.org/W1968378356","https://openalex.org/W1968441942","https://openalex.org/W1969447019","https://openalex.org/W1969939279","https://openalex.org/W1970328528","https://openalex.org/W1970338715","https://openalex.org/W1970974410","https://openalex.org/W1974139741","https://openalex.org/W1975449649","https://openalex.org/W1976428700","https://openalex.org/W1976686277","https://openalex.org/W1976726320","https://openalex.org/W1978117435","https://openalex.org/W1979088026","https://openalex.org/W1980857453","https://openalex.org/W1981135463","https://openalex.org/W1981655068","https://openalex.org/W1982168210","https://openalex.org/W1982189992","https://openalex.org/W1982933055","https://openalex.org/W1984150038","https://openalex.org/W1984429541","https://openalex.org/W1984519768","https://openalex.org/W1985370989","https://openalex.org/W1986256219","https://openalex.org/W1986587815","https://openalex.org/W1989205333","https://openalex.org/W1989296689","https://openalex.org/W1990095100","https://openalex.org/W1990933176","https://openalex.org/W1991830326","https://openalex.org/W1992845429","https://openalex.org/W1993418815","https://openalex.org/W1994963086","https://openalex.org/W1996709343","https://openalex.org/W1997131908","https://openalex.org/W2000694974","https://openalex.org/W2001361004","https://openalex.org/W2001626727","https://openalex.org/W2001779049","https://openalex.org/W2003519013","https://openalex.org/W2004328907","https://openalex.org/W2006777514","https://openalex.org/W2008960002","https://openalex.org/W2009148489","https://openalex.org/W2009414365","https://openalex.org/W2009700046","https://openalex.org/W2010087085","https://openalex.org/W2010577277","https://openalex.org/W2011818634","https://openalex.org/W2012914109","https://openalex.org/W2013706715","https://openalex.org/W2017871510","https://openalex.org/W2018923286","https://openalex.org/W2019449356","https://openalex.org/W2019463117","https://openalex.org/W2020410964","https://openalex.org/W2020983524","https://openalex.org/W2021347985","https://openalex.org/W2021600424","https://openalex.org/W2022118090","https://openalex.org/W2024135550","https://openalex.org/W2025441457","https://openalex.org/W2025851689","https://openalex.org/W2026542689","https://openalex.org/W2027415701","https://openalex.org/W2028702404","https://openalex.org/W2030911680","https://openalex.org/W2031193867","https://openalex.org/W2031195272","https://openalex.org/W2031380942","https://openalex.org/W2031444002","https://openalex.org/W2031899050","https://openalex.org/W2031939553","https://openalex.org/W2032906278","https://openalex.org/W2033319153","https://openalex.org/W2034038074","https://openalex.org/W2034911894","https://openalex.org/W2036164824","https://openalex.org/W2036405416","https://openalex.org/W2037755687","https://openalex.org/W2038484394","https://openalex.org/W2039102208","https://openalex.org/W2040115981","https://openalex.org/W2040836201","https://openalex.org/W2041570550","https://openalex.org/W2041713157","https://openalex.org/W2043336999","https://openalex.org/W2044439784","https://openalex.org/W2044924856","https://openalex.org/W2045324074","https://openalex.org/W2046454981","https://openalex.org/W2046990636","https://openalex.org/W2047605827","https://openalex.org/W2050088151","https://openalex.org/W2051291943","https://openalex.org/W2052168193","https://openalex.org/W2054332795","https://openalex.org/W2055859583","https://openalex.org/W2056194258","https://openalex.org/W2056754627","https://openalex.org/W2056942156","https://openalex.org/W2057359173","https://openalex.org/W2057847302","https://openalex.org/W2060198845","https://openalex.org/W2060630299","https://openalex.org/W2061234826","https://openalex.org/W2064711537","https://openalex.org/W2067489401","https://openalex.org/W2067854585","https://openalex.org/W2071035219","https://openalex.org/W2071041688","https://openalex.org/W2071199281","https://openalex.org/W2072318687","https://openalex.org/W2074438676","https://openalex.org/W2074832397","https://openalex.org/W2076021360","https://openalex.org/W2076749176","https://openalex.org/W2077792958","https://openalex.org/W2080287036","https://openalex.org/W2081147939","https://openalex.org/W2081827620","https://openalex.org/W2083154566","https://openalex.org/W2084252557","https://openalex.org/W2088011239","https://openalex.org/W2088483796","https://openalex.org/W2089906643","https://openalex.org/W2090195452","https://openalex.org/W2092580882","https://openalex.org/W2093723806","https://openalex.org/W2094916229","https://openalex.org/W2095160367","https://openalex.org/W2098223144","https://openalex.org/W2098644908","https://openalex.org/W2098806204","https://openalex.org/W2102464818","https://openalex.org/W2103230017","https://openalex.org/W2103775523","https://openalex.org/W2105083581","https://openalex.org/W2105525798","https://openalex.org/W2106623534","https://openalex.org/W2107272456","https://openalex.org/W2108116605","https://openalex.org/W2110826367","https://openalex.org/W2111180132","https://openalex.org/W2111806948","https://openalex.org/W2112078762","https://openalex.org/W2112532834","https://openalex.org/W2114207292","https://openalex.org/W2117770689","https://openalex.org/W2118053238","https://openalex.org/W2120087347","https://openalex.org/W2122532823","https://openalex.org/W2126022125","https://openalex.org/W2126109667","https://openalex.org/W2126910886","https://openalex.org/W2127737175","https://openalex.org/W2128911488","https://openalex.org/W2129471240","https://openalex.org/W2131129488","https://openalex.org/W2132317181","https://openalex.org/W2133604289","https://openalex.org/W2133996321","https://openalex.org/W2134567364","https://openalex.org/W2137566722","https://openalex.org/W2139124373","https://openalex.org/W2139473713","https://openalex.org/W2140795762","https://openalex.org/W2145653235","https://openalex.org/W2146715636","https://openalex.org/W2151246967","https://openalex.org/W2153000307","https://openalex.org/W2153141931","https://openalex.org/W2155440953","https://openalex.org/W2155578687","https://openalex.org/W2155598961","https://openalex.org/W2157738629","https://openalex.org/W2159570527","https://openalex.org/W2159594827","https://openalex.org/W2160553642","https://openalex.org/W2160762156","https://openalex.org/W2161738096","https://openalex.org/W2161931612","https://openalex.org/W2165022559","https://openalex.org/W2165099173","https://openalex.org/W2178557511","https://openalex.org/W2249096125","https://openalex.org/W2265277925","https://openalex.org/W2269558099","https://openalex.org/W2288413791","https://openalex.org/W2315618879","https://openalex.org/W2322095705","https://openalex.org/W2324841714","https://openalex.org/W2329306090","https://openalex.org/W2337516302","https://openalex.org/W2398136270","https://openalex.org/W2410274230","https://openalex.org/W2419416993","https://openalex.org/W2473253444","https://openalex.org/W2505312274","https://openalex.org/W2885558644","https://openalex.org/W2917148411","https://openalex.org/W2917922799","https://openalex.org/W3023642540","https://openalex.org/W3142695843","https://openalex.org/W3144816857"],"related_works":["https://openalex.org/W2095816971","https://openalex.org/W1998760541","https://openalex.org/W2904004003","https://openalex.org/W3036878513","https://openalex.org/W622674477","https://openalex.org/W2094377607","https://openalex.org/W7216856492","https://openalex.org/W4281563016","https://openalex.org/W4413833674","https://openalex.org/W2972232451"],"abstract_inverted_index":{"RHO":[0,21,48,62,70,125,358,370,383],"family":[1,49,126,384],"proteins":[2,385],"control":[3],"cell":[4,305],"movement":[5],"and":[6,14,59,73,84,119,122,165,187,189,207,209,235,268,271,319,322,329,361,390,393],"intracellular":[7],"signaling":[8,19,389],"by":[9,113,176,218,335],"cycling":[10],"between":[11],"active":[12,341],"GTP-bound":[13,220,342],"inactive":[15],"GDP-bound":[16],"states.":[17],"Aberrant":[18],"of":[20,46,61,101,116,124,141,146,152,183,204,212,251,274,285,311,324,382],"GTPases":[22],"has":[23,75],"been":[24,76],"implicated":[25],"in":[26,132,160,245,253,288,339,344,386],"many":[27],"diseases":[28],"including":[29],"cancer":[30,83],"and\\ninflammation.":[31],"Geranylgeranyltransferase":[32],"type":[33],"I":[34,151],"(GGTase-I)":[35],"attaches":[36],"a":[37,42,79,278,282],"20-carbon":[38],"geranylgeranyl":[39,117],"lipid":[40],"to":[41,67,81,111,169,201,266,291,308],"carboxyl-terminal":[43],"CAAX":[44],"motif":[45],"most":[47],"proteins.":[50,63,127],"\\nGeranylgeranylation":[51],"is":[52,355],"viewed":[53],"as":[54,78],"essential":[55,356],"for":[56,357],"membrane":[57],"targeting":[58],"activation":[60,203,360],"Consequently,":[64],"inhibiting":[65],"GGTase-I":[66,159,198,230,243,294],"interfere":[68],"with":[69,193],"protein":[71,359,371],"lipidation":[72],"activity":[74,321],"proposed":[77],"strategy":[80],"treat":[82],"inflammatory":[85,388],"disorders.":[86],"Moreover,":[87,197],"statins":[88],"\u2013":[89,94,277],"widely":[90],"prescribed":[91],"cholesterol-lowering":[92,103],"drugs":[93],"possess":[95],"anti-inflammatory":[96,227],"properties":[97],"that":[98,156,259,280,353,363],"are":[99,109],"independent":[100],"their":[102],"effects.":[104,398],"These":[105],"pleiotropic":[106,396],"statin":[107,397],"effects":[108],"thought":[110],"be\\nmediated":[112],"reduced":[114,120,297],"synthesis":[115],"lipids":[118],"geranylgeranylation":[121,354],"inhibition":[123],"Despite":[128],"the":[129,139,194,249,272,325,340,345,350,380],"therapeutic":[130],"interest":[131],"GGTase-I,":[133],"no":[134],"studies":[135],"have":[136],"yet":[137],"defined":[138],"impact":[140],"inactivating":[142],"GGTase-I\\nin":[143],"mouse":[144],"models":[145],"inflammation":[147,164,234,270],"using":[148],"genetic":[149],"strategies.\\nPaper":[150],"this":[153,364],"thesis":[154,348,374],"shows":[155],"mice":[157,232],"lacking":[158],"macrophages":[161,178,246],"develop":[162],"joint":[163],"bone":[166],"erosions":[167],"similar":[168],"rheumatoid":[170,275],"arthritis.":[171],"The":[172,331,373],"disease":[173,279],"was":[174,333],"initiated":[175],"GGTase-I-deficient":[177],"which":[179,337],"accumulated":[180,338],"high":[181,283,309],"levels":[182,310],"GTPbound":[184],"RAC1,":[185],"CDC42,":[186],"RHOA,":[188],"RAC1":[190],"remained":[191],"associated":[192],"plasma":[195],"membrane.":[196],"deficiency":[199,244,295],"led":[200],"robust":[202],"p38":[205],"MAPK":[206],"NF-\u03baB,":[208],"increased":[210,317],"production":[211],"proinflammatory":[213],"cytokines.":[214],"This":[215],"effect":[216],"was\\ncaused":[217],"non-geranylgeranylated":[219],"RAC1.":[221],"Thus,":[222],"rather":[223],"than":[224],"being":[225],"an":[226],"drug":[228],"target,":[229],"protects":[231],"from":[233],"arthritis":[236,276],"development.\\nIn":[237],"Paper":[238],"II,":[239],"we":[240],"tested":[241],"if":[242],"would":[247,262],"affect":[248],"development":[250,287],"atherosclerosis":[252,286,298],"LDL":[254],"receptor\u2013deficient":[255],"mice.":[256],"We":[257],"hypothesized":[258],"aortic":[260],"lesions":[261],"be":[263],"enhanced":[264],"due":[265,307],"local":[267],"systemic":[269],"presence":[273],"carries":[281],"risk":[284],"humans.":[289],"Contrary":[290],"our":[292],"expectations,":[293],"markedly":[296],"development.":[299],"Cellular":[300],"analyses":[301,315],"revealed":[302,316],"impaired":[303],"foam":[304],"formation":[306],"cholesterol":[312,391],"efflux.":[313],"Molecular":[314],"COX2":[318],"PPAR\u03b3":[320],"expression":[323],"scavenger":[326],"receptors":[327],"CD36":[328],"SR-B1.":[330],"pathway":[332],"triggered":[334],"RHOA":[336],"state":[343],"GGTase-I-deficient\\nmacrophages.":[346],"\\nThis":[347],"challenges":[349],"current":[351],"dogma":[352],"suggest":[362],"posttranslational":[365],"modification":[366],"may":[367],"actually":[368],"inhibit":[369],"function.":[372],"also":[375],"sheds":[376],"new":[377],"light":[378],"on":[379],"role":[381],"macrophage":[387],"homeostasis":[392],"mechanisms":[394],"underlying":[395]},"counts_by_year":[],"updated_date":"2026-08-30T07:30:35.949966","created_date":"2016-06-24T00:00:00"}
