Cov khoom

Ib qho kev hloov pauv ntawm ABL1 noob mus rau BCR cov noob tau tshwm sim hauv kev qhia ntawm oncogenic BCR-ABL1 fusion protein, uas ua rau tib neeg mob myeloid leukemia (CML), myeloproliferative teeb meem suav tias tsis muaj kev tuag mus txog thaum kev qhia txog tsev neeg imatinib ntawm tyrosine kinase. inhibitors (TKI).Txawm li cas los xij, insensitivity ntawm CML qia hlwb rau TKI kev kho mob thiab intrinsic los yog tau txais kuj tseem yog nquag ua rau cov kab mob persistence thiab blastic theem kev loj hlob nyob rau hauv cov neeg mob tom qab thawj zaug kev vam meej kev kho mob.Ntawm no, peb tau tshawb xyuas lub luag haujlwm ua tau rau MAPK15 / ERK8 kinase hauv BCR-ABL1-dependent autophagy, txheej txheem tseem ceeb rau oncogene-induced leukemogenesis.Hauv cov ntsiab lus no, peb tau pom lub peev xwm ntawm MAPK15 rau lub cev nrhiav cov oncogene rau autophagic vesicles, lees paub peb qhov kev xav ntawm lub luag haujlwm lom neeg rau lub cev MAP kinase hauv cov teeb liab hloov pauv los ntawm oncogene no.Tseeb tiag, los ntawm kev ua qauv qhia BCR-ABL1 hauv HeLa hlwb thiab ua kom zoo dua ntawm tus qauv tsim nyog rau tib neeg CML, piv txwv li K562 hlwb, peb tau pom tias BCR-ABL1-induced autophagy yog kho los ntawm MAPK15 los ntawm nws lub peev xwm los cuam tshuam nrog LC3-tsev neeg. cov proteins, nyob rau hauv LIR-dependent yam.Interestingly, peb kuj muaj peev xwm cuam tshuam nrog BCR-ABL1-induced autophagy los ntawm ib tug kws kho mob mus kom ze rau inhibiting MAPK15, qhib qhov muaj peev xwm ntawm kev ua ntawm no kinase cuam tshuam rau autophagy thiab kab mob nyob ntawm no cellular function.Tseeb, los txhawb qhov ua tau ntawm txoj hauv kev no, peb tau pom tias kev txo qis ntawm endogenous MAPK15 qhia inhibited BCR-ABL1-dependent cell proliferation, in vitro, thiab qog tsim, hauv vivo, yog li muab cov tshiab "druggable" txuas ntawm BCR-ABL1 thiab human CML.