Ibicuruzwa

Guhinduranya gene ya ABL1 kuri gene ya BCR bivamo kwerekana proteine ​​ya oncogenic BCR-ABL1 fusion protein, iranga indwara ya myeloid leukemia yumuntu (CML), indwara ya myeloproliferative ifatwa nkimpfu zica kugeza igihe umuryango wa imatinib wa tyrosine kinase utangiriye inhibitor (TKI).Nubwo bimeze bityo ariko, kutumva ingirabuzimafatizo ya CML kubuvuzi bwa TKI no kurwanya imbere cyangwa kurwanywa biracyari impamvu zitera indwara no gukomeza gutera intambwe igaragara kubarwayi nyuma yo kuvurwa neza.Hano, twasesenguye uruhare rushoboka kuri MAPK15 / ERK8 kinase muri BCR-ABL1 iterwa na autophagy, inzira yingenzi ya leukemogenezi iterwa na oncogene.Ni muri urwo rwego, twerekanye ubushobozi bwa MAPK15 bwo kwinjiza umubiri wa oncogene mu mitsi ya autophagic, twemeza hypothesis yacu uruhare rwibinyabuzima kuri iyi MAP kinase mugukwirakwiza ibimenyetso niyi oncogene.Mubyukuri, mugushushanya BCR-ABL1 amarenga muri selile ya HeLa hamwe ninyungu zingirakamaro zifatika zifatika kubantu ba CML, ni ukuvuga selile K562, twerekanye ko autophagy iterwa na BCR-ABL1 yunganirwa na MAPK15 binyuze mubushobozi bwayo bwo gukorana numuryango LC3. poroteyine, mu buryo bwa LIR.Igishimishije, twashoboye kandi kwivanga muri autofagy iterwa na BCR-ABL1 hakoreshejwe uburyo bwa farumasi bugamije kubuza MAPK15, gufungura amahirwe yo gukora kuri iyi kinase kugira ngo bigire ingaruka kuri autofagy n'indwara bitewe niyi mikorere ya selile.Mubyukuri, kugirango dushyigikire uburyo bwubu buryo, twerekanye ko kugabanuka kwimvugo ya MAPK15 ya endogenous yabujije ikwirakwizwa rya selile iterwa na BCR-ABL1, muri vitro, no kubyimba ibibyimba, muri vivo, bityo bitanga igitekerezo gishya "ibiyobyabwenge" hagati ya BCR-ABL1 na muntu CML.