Imikhiqizo

Ukudluliselwa okuhambisanayo kofuzo lwe-ABL1 kuya kufuzo lwe-BCR kuphumela ekuvezweni kwe-oncogenic BCR-ABL1 fusion protein, ebonisa i-human chronic myeloid leukemia (CML), isifo se-myeloproliferative esibhekwa njengesibulalayo ngokungaguquki kuze kube kwethulwa umndeni we-imatinib we-tyrosine kinase. ama-inhibitors (TKI).Noma kunjalo, ukungezwani kwamaseli e-CML stem ekwelapheni kwe-TKI kanye nokumelana kwangaphakathi noma okutholiwe kuseyizimbangela ezivamile zokuphikelela kwezifo kanye nokuqhubekela phambili kwesigaba se-blastic okuhlangenwe nakho ezigulini ngemva kokwelashwa okuphumelelayo kokuqala.Lapha, siphenye indima engaba khona ye-MAPK15/ERK8 kinase ku-BCR-ABL1-dependent autophagy, inqubo eyinhloko ye-leukemogenesis ebangelwa i-oncogene.Kulo mongo, sibonise ikhono le-MAPK15 lokubuthela ngokoqobo i-oncogene kuma-autophagic vesicles, eqinisekisa umbono wethu wendima ehlobene ngokwebhayoloji yale MAP kinase ekudluliselweni kwesignali ngale oncogene.Ngempela, ngokumodela ukusayina kwe-BCR-ABL1 kumaseli e-HeLa kanye nokusebenzisa imodeli efanele ngokomzimba ye-CML yomuntu, okungukuthi amaseli e-K562, sibonise ukuthi i-BCR-ABL1-induced autophagy is mediated by MAPK15 ngokusebenzisa ikhono layo lokusebenzelana ne-LC3-family. amaprotheni, ngendlela encike ku-LIR.Kuyathakazelisa ukuthi siphinde sakwazi ukuphazamisa i-BCR-ABL1-induced autophagy ngendlela ye-pharmacological okuhloswe ngayo ukuvimbela i-MAPK15, okuvula ithuba lokuthatha isinyathelo ngale kinase ukuze kuthinteke i-autophagy nezifo kuye ngalo msebenzi weselula.Ngempela, ukusekela ukuba nokwenzeka kwale ndlela, sibonise ukuthi ukuncipha kwenkulumo ye-MAPK15 engapheli kuvimbela ukwanda kwamaseli ancike ku-BCR-ABL1, i-in vitro, nokwakheka kwesimila, ku-vivo, ngakho-ke kuhlinzeka ngesixhumanisi "esidakwayo" esiphakathi kwe-BCR-ABL1 kanye CML yomuntu.