Hua

Ko te whakawhitinga tauutuutu o te ira ABL1 ki te ira BCR ka puta te whakaputanga o te oncogenic BCR-ABL1 pūmua whakakotahi, e tohu ana i te reukemia myeloid mau tonu o te tangata (CML), he mate myeloproliferative e kiia ana he mate mate tae noa ki te whakaurunga o te whanau imatinib o tyrosine kinase. aukati (TKI).Heoi ano, ko te koretake o nga pūtau kakau CML ki te maimoatanga TKI me te atete o roto, kua riro mai ranei, he maha tonu nga take mo te mau tonu o te mate me te haere tonutanga o te wahanga ngongo i roto i nga turoro i muri i nga rongoatanga angitu tuatahi.I konei, i tirotirohia e matou he mahi pea mo te kinase MAPK15/ERK8 i roto i te autophagy whakawhirinaki BCR-ABL1, he mahinga matua mo te leukemogenesis oncogene-induced.I roto i tenei horopaki, i whakaatuhia e matou te kaha o te MAPK15 ki te tango tinana i te oncogene ki nga vesicles autophagic, e whakapumau ana i to maatau whakaaro mo te mahi koiora mo tenei kinase MAP i roto i te whakawhiti tohu e tenei oncogene.Ae, na te whakatauira i te tohu BCR-ABL1 i roto i nga pūtau HeLa me te painga o tetahi tauira e pa ana ki te tinana mo te CML tangata, ara, nga pūtau K562, i whakaatuhia e matou ko te autophagy-induced BCR-ABL1 he takawaenga e MAPK15 na roto i tona kaha ki te taunekeneke me te LC3-whanau. pūmua, i roto i te tikanga e whakawhirinaki ana ki te LIR.He mea whakamiharo, i taea ano e matou te pokanoa ki te BCR-ABL1-induced autophagy e te huarahi rongoa e whai ana ki te aukati i te MAPK15, ka whakatuwhera i te kaha ki te mahi i tenei kinase ki te pa ki te autophagy me nga mate i runga i tenei mahi pūkoro.Ae, ki te tautoko i te whaihuatanga o tenei huarahi, i whakaatuhia e matou ko te whakahekenga o te whakaaturanga MAPK15 endogenous i aukati i te tipu o te pūtau e whakawhirinaki ana ki te BCR-ABL1, i roto i te vitro, me te hanga puku, i roto i te vivo, na reira ka whakarato i tetahi hononga hou "taakaro" i waenga i te BCR-ABL1 me tangata CML.