Stk11 C-Terminal domain variants impact lung cancer biology independent of kinase activity
Nandagopal, Gopika
Nandagopal, Gopika
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Abstract
STK11 mutations in KRAS-driven lung adenocarcinomas (LUADs) are associated with aggressive tumors characterized by increased risk of metastasis. STK11 is a master kinase comprised of an N-terminal, kinase, and a non-catalytic C-terminal domain (CTD). CTD Missense mutations are prevalent and often characterized as variants of unknown significance, due to their unobstructed kinase activity. We propose the use of a multi-pronged functional assessment strategy to characterize these variants as benign or pathogenic. Current work has identified the CTD polybasic motif as key for STK11 localisation. Immunofluorescent microscopy shows that missense variants at these residues are retained in the nucleus.
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Graduate
Date
2024-01-01