Article
Exploiting the intrinsic misfolding propensity of the KRAS oncoprotein.
Proceedings of the National Academy of Sciences of the United States of America - 28 Feb 2023
Janssen Kobe, Claes Filip, Van de Velde Dido, Wehbi Vanessa L, Houben Bert, Lampi Yulia, Nys Mieke, Khodaparast Laleh, Khodaparast Ladan, Louros Nikolaos, van der Kant Rob, Verniers Joffre, Garcia Teresa, Ramakers Meine, Konstantoulea Katerina, Maragkou Katerina, Duran-Romaña Ramon, Musteanu Mónica, Barbacid Mariano, Scorneaux Bernard, Beirnaert Els, Schymkowitz Joost, Rousseau Frederic
Abstract excerpt
Mutant KRAS is a major driver of oncogenesis in a multitude of cancers but remains a challenging target for classical small molecule drugs, motivating the exploration of alternative approaches. Here, we show that aggregation-prone regions (APRs) in the primary sequence of the oncoprotein constitute intrinsic vulnerabilities that can be exploited to misfold KRAS into protein aggregates. Conveniently, this...
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