作者
Qianhe Zhou, Adnan Derti, David Ruddy, Daniel Rakiec, Iris Kao, Michelle Lira, Veronica Gibaja, HoMan Chan, Yi Yang, Junxia Min, Michael R Schlabach, Frank Stegmeier
发表日期
2015/5/15
期刊
Cancer research
卷号
75
期号
10
页码范围
1949-1958
出版商
American Association for Cancer Research
简介
Assessing the functional significance of novel putative oncogenes remains a significant challenge given the limitations of current loss-of-function tools. Here, we describe a method that employs TALEN or CRISPR/Cas9-mediated knock-in of inducible degron tags (Degron-KI) that provides a versatile approach for the functional characterization of novel cancer genes and addresses many of the shortcomings of current tools. The Degron-KI system allows for highly specific, inducible, and allele-targeted inhibition of endogenous protein function, and the ability to titrate protein depletion with this system is able to better mimic pharmacologic inhibition compared with RNAi or genetic knockout approaches. The Degron-KI system was able to faithfully recapitulate the effects of pharmacologic EZH2 and PI3Kα inhibitors in cancer cell lines. The application of this system to the study of a poorly understood putative …
学术搜索中的文章
Q Zhou, A Derti, D Ruddy, D Rakiec, I Kao, M Lira… - Cancer research, 2015