[Mechanisms of recombinant adenovirus-mediated SD-HA fusion protein proliferation inhibition and induced apoptosis of K562 cells].
Zhonghua Xue Ye Xue Za Zhi
; 39(4): 314-319, 2018 Apr 14.
Article
in Zh
| MEDLINE
| ID: mdl-29779329
ABSTRACT
Objective:
To investigate whether fusion protein SD-HA could regulate its downstream signaling molecule activity by competing with the phospho-BCR-ABL Y177 site, and its mechanisms to inhibit proliferation and induce apoptosis of K562 cells.Methods:
Co-immunoprecipitation interaction technology analysis of fusion protein SD-HA functioned by potently binding to the phospho-BCR-ABL Y177 site, Ras, MAPK and Akt activities were observed in the Ad5F35-SD-HA-treated cells. Western blot analyses of SD-HA fusion protein on cell membrane receptor pathway to death cascade caspase-8, caspase-3 and PRAP were performed.Results:
Exploration into the underlying mechanisms revealed that Ad5F35-SD-HA infection functioned by binding to the phospho-BCR-ABL Y177 site, which lead to a complex with Grb2. competitively disrupted the Grb2 SH2-phospho-BCR-ABL Y177 formation. The fusion protein SD-HA could reduce the activation of Ras and phosphorylation of MAPK (p-MAPK) and the expression level of p-ELK, inhibition of Ras-MAPK signaling pathway; SD-HA fusion protein could reduce p-Akt and Akt substrate p-GSK with inhibition of PI3K-Akt signaling pathway, thereby inhibiting the proliferation of K562 cells. Caspases-8-induced apoptosis signal could be activated by DED protein binding to DED domain of precursor caspases-8.Conclusions:
The strategy of fusion protein SD-HA inhibiting-Y177 BCR-ABL and Grb2 binding could be used as a novel entry point for the treatment of chronic myeloid leukemia.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apoptosis
/
Cell Proliferation
Limits:
Humans
Language:
Zh
Journal:
Zhonghua Xue Ye Xue Za Zhi
Year:
2018
Document type:
Article