Kayayyaki

Matsakaicin madaidaicin kwayar halittar ABL1 zuwa kwayoyin halittar BCR yana haifar da bayyanar da furotin na BCR-ABL1 na oncogenic, wanda ke nuna cutar sankarar jini ta myeloid na ɗan adam (CML), cuta ce ta myeloproliferative da aka yi la’akari da ita mai mutuwa har sai an gabatar da dangin imatinib na tyrosine kinase. masu hanawa (TKI).Duk da haka, rashin jin daɗin ƙwayoyin ƙwayoyin ƙwayoyin cuta na CML zuwa jiyya na TKI da juriya na ciki ko samun juriya har yanzu sune dalilai masu yawa don dawwamar cuta da ci gaban lokaci mai fashewa da aka samu a cikin marasa lafiya bayan nasarar farfaɗowar farko.Anan, mun bincika yiwuwar yiwuwar MAPK15 / ERK8 kinase a cikin BCR-ABL1-dogara autophagy, wani mahimmin tsari don cutar sankarar mahaifa ta haifar da oncogene.A cikin wannan mahallin, mun nuna ikon MAPK15 don ɗaukar oncogene ta jiki zuwa vesicles na autophagic, yana tabbatar da hasashenmu na rawar da ta dace ta ilimin halitta don wannan MAP kinase a cikin siginar siginar ta wannan oncogene.Tabbas, ta hanyar yin siginar BCR-ABL1 a cikin ƙwayoyin HeLa da kuma amfani da fa'idar samfurin da ya dace da tsarin ilimin halittar jiki don CML ɗan adam, watau K562 Kwayoyin, mun nuna cewa BCR-ABL1-induced autophagy yana shiga tsakani ta hanyar MAPK15 ta hanyar ikon yin hulɗa tare da LC3-iyali. sunadaran, ta hanyar dogaro da LIR.Abin sha'awa shine, mun kuma sami damar tsoma baki tare da BCR-ABL1-induced autophagy ta hanyar maganin magunguna da nufin hana MAPK15, buɗe yiwuwar yin aiki akan wannan kinase don rinjayar autophagy da cututtuka dangane da wannan aikin salula.Lallai, don tallafawa yuwuwar wannan hanyar, mun nuna cewa raguwar maganganun MAPK15 mai ƙarewa ya hana haɓakar ƙwayoyin cuta masu dogaro da BCR-ABL1, in vitro, da ƙari, a cikin vivo, don haka samar da wata hanyar haɗin gwiwa ta "druggable" labari tsakanin BCR-ABL1 da mutum CML.