PXD046277-1

PXD046277 is an original dataset announced via ProteomeXchange.

Title	Pharmacological Targeting of Casein Kinase 1δ Suppresses Oncogenic NRAS-Driven Melanoma
Description	Activating mutations in NRAS account for 20-30% of melanoma, yet effective anti-NRAS therapies are still lacking. In this study, we unveil the casein kinase 1δ (CK1δ) as an uncharacterized regulator of oncogenic NRAS mutations, specifically Q61R and Q61K, which are the most prevalent NRAS mutations in melanoma. The genetic ablation or pharmacological inhibition of CK1δ markedly destabilizes NRAS mutants and suppresses their oncogenic functions. Moreover, we identify USP46 as a bona fide deubiquitinase of NRAS mutants. Mechanistically, CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity towards NRAS mutants, thus promoting oncogenic NRAS-driven melanocyte malignant transformation and melanoma progression in vitro and in vivo. Our findings underscore the significance of the CK1δ-USP46 axis in stabilizing oncogenic NRAS mutants and provide preclinical evidence that targeting this axis holds promise as a therapeutic strategy for human melanoma harboring NRAS mutations.
HostingRepository	PRIDE
AnnounceDate	2024-09-20
AnnouncementXML	Submission_2024-09-19_20:49:53.909.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	yalei wen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-20 21:04:35	ID requested
⏵ 1	2024-09-19 20:49:54	announced

Dataset with its publication pending

submitter keyword: Oncogenic NRAS；melanomagenesis； melanoma progression CK1δ； USP46.

Tongzheng Liu
contact affiliation	3. College of Pharmacy / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China
contact email	liutongzheng@jnu.edu.cn
lab head
yalei wen
contact affiliation	Guangdong Second Provincial General Hospital, Postdoctoral Station of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou 510632, China
contact email	491574395@qq.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD046277

PRIDE project URI

• PRIDE
  1. PXD046277
     1. Label: PRIDE project
     2. Name: Pharmacological Targeting of Casein Kinase 1δ Suppresses Oncogenic NRAS-Driven Melanoma