The N-terminal domain of the non-receptor tyrosine kinase ABL confers protein instability and suppresses tumorigenesis
The N-terminal domain of the non-receptor tyrosine kinase ABL confers protein instability and suppresses tumorigenesis
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非受体酪氨酸激酶 ABL 的 N 端结构域赋予蛋白质稳定性并抑制肿瘤发生
DOI：
10.1074/jbc.ra120.012821
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发表时间：
2020-05
影响因子：
4.8
通讯作者：
Hai Rao
中科院分区：
文献类型：
--
作者：
Zhengwei Yan;Karthigayan Shanmugasundaram;Dongwen Ma;Jiayu Luo;Shiwen Luo;Hai Rao
Chromosome translocation can lead to chimeric proteins that may become oncogenic drivers. A classic example is the fusion of the BCR activator of RhoGEF and GTPase and the ABL proto-oncogene nonreceptor tyrosine kinase, a result of a chromosome abnormality (Philadelphia chromosome) that causes leukemia. To unravel the mechanism underlying BCR-ABL–mediated tumorigenesis, here we compared the stability of ABL and the BCR-ABL fusion. Using protein degradation, cell proliferation, 5-ethynyl-2-deoxyuridine, and apoptosis assays, along with xenograft tumor analysis, we found that the N-terminal segment of ABL, which is lost in the BCR-ABL fusion, confers degradation capacity that is promoted by SMAD-specific E3 ubiquitin protein ligase 1. We further demonstrate that the N-terminal deletion renders ABL more stable and stimulates cell growth and tumorigenesis. The findings of our study suggest that altered protein stability may contribute to chromosome translocation-induced cancer development.
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影响因子：
78.5
作者：
T. O'hare;M. Zabriskie;A. Eiring;M. Deininger
通讯作者：
T. O'hare;M. Zabriskie;A. Eiring;M. Deininger
影响因子：
12.4
作者：
Coppola, S;Narciso, L;Peschle, C
通讯作者：
Peschle, C
影响因子：
28.2
作者：
Asmussen J;Lasater EA;Tajon C;Oses-Prieto J;Jun YW;Taylor BS;Burlingame A;Craik CS;Shah NP
通讯作者：
Shah NP
影响因子：
9.2
作者：
Echarri, A;Pendergast, AM
通讯作者：
Pendergast, AM
DOI：
10.1038/nrc.2017.105
发表时间：
2018-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Senft D;Qi J;Ronai ZA
通讯作者：
Ronai ZA