A Human Protein Interaction Network Shows Conservation of Aging Processes between Human and Invertebrate Species 英文参考文献.docVIP

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A Human Protein Interaction Network Shows Conservation of Aging Processes between Human and Invertebrate Species 英文参考文献.doc

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A Human Protein Interaction Network Shows Conservation of Aging Processes between Human and Invertebrate Species 英文参考文献

AHumanProteinInteractionNetworkShows ConservationofAgingProcessesbetweenHumanand InvertebrateSpecies RussellBell1.,AlanHubbard2,3.,RakeshChettier1.,DiChen3,JohnP.Miller3,PankajKapahi3 ,Mark Tarnopolsky4,SudhirSahasrabuhde1,SimonMelov3,RobertE.Hughes3* 1ProlexysPharmaceuticals,SaltLakeCity,Utah,UnitedStatesofAmerica,2SchoolofPublicHealth,UniversityofCaliforniaBerkeley,Berkeley,California,UnitedStatesof America,3BuckInstituteforAgeResearch,Novato,California,UnitedStatesofAmerica,4McMasterUniversityMedicalCenter,Hamilton,Ontario,Canada Abstract We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional humanproteinsthatinteractwiththesehomologs.Overall,thenetworkconsistsof3,271binaryinteractionsamong2,338 uniqueproteins.Acomparisonoftheaveragenodedegreeofthehumanlongevityhomologswithrandomsetsofproteins intheCoreNetworkindicatesthathumanhomologsoflongevityproteinsarehighlyconnectedhubswithameannode degreeof18.8partners.Shortestpathlengthanalysisshowsthatproteinsinthisnetworkaresignificantlymoreconnected thanwouldbeexpectedbychance.Toexaminetherelationshipofthisnetworktohumanagingphenotypes,wecompared thegenesencodinglongevitynetworkproteinstogenesknowntobechangedtranscriptionallyduringaginginhuman muscle.Inthecaseofboththelongevityproteinhomologsandtheirinteractors,weobservedenrichmentsfordifferentially expressedgenesinthenetwork.Todeterminewhetherhomologsofhumanlongevityinteractingproteinscanmodulate lifespanininvertebrates,homologsof18humanFRAP1interactingproteinsshowingsignificantchangesinhumanaging muscle were tested for effects on nematode life span using RNAi. Of 18 genes