PXD029725-2

PXD029725 is an original dataset announced via ProteomeXchange.

Title	Oncogenic Mutations of KRAS Modulate Its Turnover by the CUL3/LZTR1 E3 ligase Complex
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:32:21.556.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Svenja Hester
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-12 07:04:35	ID requested
1	2024-03-06 10:16:51	announced
⏵ 2	2024-10-22 06:32:21	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: G13D,KRAS, G12D

Andreas Damianou
contact affiliation	Nuffield Department of Medicine
contact email	andreas.damianour@ndm.ox.ac.uk
lab head
Svenja Hester
contact affiliation	Nuffield Department of Medicine
contact email	svenja.hester@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029725
     1. Label: PRIDE project
     2. Name: Oncogenic Mutations of KRAS Modulate Its Turnover by the CUL3/LZTR1 E3 ligase Complex