Naslov
D154Q Mutation does not Alter KRAS Dimerization

Autori
Grozavu, Ingrid ; Stuart, Sarah ; Lyakisheva, Anna ; Yao, Zhong ; Pathmanathan, Shivanthy ; Ohh, Michael ; Štagljar, Igor

Izvornik
Journal of molecular biology (0022-2836) 434 (2022), 2; 167392, 8

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
KRAS ; dimerization ; MaMTH ; SIMPL ; co-immunoprecipitation ; Oncogenic signalling ; Cancer therapeutics

Sažetak
KRAS is one of the most frequently mutated oncogenes in human cancers. Despite nearly 40 years of research, KRAS remains largely undruggable, in part due to an incomplete understanding of its biology. Recently, KRAS dimerization was discovered to play an important role in its signalling function. The KRAS D154Q mutant was described as a dimer-deficient variant that can be used to study the effect of dimer- ization in KRAS oncogenicity. However, we show here that KRAS D154Q homo-and heterodimerized with KRAS WT using three separate protein-protein interaction assays, and that oncogenic KRAS dimer- ization was not negatively impacted by the presence of a secondary D154Q mutation. In conclusion, we advise caution in using this variant to study the purpose of dimerization in KRAS oncogenic behaviour.(c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://crea-tivecommons.org/licenses/by-nc- nd/4.0/).

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA