Oncogenic Mutations of KRAS Modulate Its Turnover by the CUL3/LZTR1 E3 ligase Complex
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ABSTRACT: KRAS is a proto-oncogene encoding a small GTPase. Mutations contribute up to 30% of human solid tumours including lung adenocarcinoma, pancreatic and colorectal carcinomas. Most KRAS activating mutations interfere with GTP hydrolysis, essential for its role as a molecular switch, leading to alterations in their molecular environment and oncogenic signalling. Here, APEX-2 proximity labelling was used to profile the molecular environment of wild type and G12D, G13D and Q61H activating mutants of KRAS under both, starvation and stimulation conditions. We demonstrate by quantitative proteomics the presence of known interactors of KRAS including a-RAF and LZTR1, which varied in abundance with wildtype and KRAS mutants. Notably, the KRAS mutations G12D, G13D and Q61H abrogate association with LZTR1. Wildtype KRAS and LZTR1, as part of the CUL3 ubiquitin E3 ligase complex, affect each other’s protein stability.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Permanent Cell Line Cell
SUBMITTER: Svenja Hester
LAB HEAD: Andreas Damianou
PROVIDER: PXD029725 | Pride | 2024-03-06
REPOSITORIES: Pride
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