Matthew Oser, Associate Professor of Medicine at Dana-Farber Cancer Institute, shared on LinkedIn:
“Thrilled to share another new study from our lab, co-led by Keita Masuzawa and Kevin Dong.
In this work, we combine genome-wide CRISPR knockout screening with base editor screening to identify regulators of ASCL1 protein abundance in SCLC and uncover a mechanism by which HUWE1 controls ASCL1 degradation through its C-terminal phospho-degron.
Beyond ASCL1, this study provides a generalizable framework for using complementary CRISPR-based screening approaches to dissect the regulation and function of lineage transcription factors in their endogenous cellular context.
Congratulations to Keita, Kevin, and everyone involved in this work!”
Nilay Sethi, Assistant Professor at Dana-Farber Cancer Institute, also highlighted the study:
“Elegant and rigorous – the only way to do science in the Oser lab.
A CRISPR screen applied to a custom reporter system identified HUWE1 as a stability regulator of ASCL1, a critical transcription factor driving a major subtype of small cell lung cancer. That’s the start. Then base editors define critical domains, including a previously uncharacterized IDR region. Well done Matthew Oser and team!”
Title: A HUWE1 regulatory helix gates ASCL1 degradation through its C-terminal phospho-degron in small cell lung cancer
Authors: Keita Masuzawa, Kevin D. Dong, Calvin XiaoYang Hu, Ting Peng, Yoochan Myung, Shilpa Singh, Xinyue Li, Tianchu Wang, Cyrus Jin, Joao A. Paulo, Ka Yang, Ernst W. Schmid, Matthew A. Booker, Yixiang Li, Deli Hong, Suzan Lazo, Michael Y. Tolstorukov, John G. Doench, Leslie Duplaquet, Katherine A. Donovan, Sumaiya Iqbal, Eric S. Fischer, Brian B. Liau, Steven P. Gygi, Matthew G. Oser.
Read the full article.
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