PXD053566

PXD053566 is an original dataset announced via ProteomeXchange.

Title	VHL acts as an adaptor to promote the phosphorylation of FTO by CK2 to suppress clear cell renal cell carcinoma
Description	Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark feature of ccRCC, a clear cell renal cell carcinoma. However, elucidating how VHL loss drives ccRCC pathogenesis remains challenging. As the most abundant posttranscriptional modification of mRNA in eukaryotes, N6-methyladenine (m6A) is involved in the posttranscriptional regulation of mRNA molecules and has been found to play an important role in the biological process of tumorigenesis and cancer progression. Here, we show that VHL has a protein interaction with the m6A demethylase FTO, but does not perform the classical function of targeting FTO for ubiquitination degradation. Rather, VHL acts as an adapter that promotes CK2 phosphorylation of FTO, thereby regulating the enzymatic activity of FTO. MeRIP-Seq and RNA-seq sequencing analyses identified EGR1 as one of the FTO targets for VHL-deficient ccRCC cell survival. Mechanistically, FTO in ccRCC decreases the m6A level of EGR1 and inhibits EGR1 and P53 protein levels, thereby promoting ccRCC proliferation. In summary, our study identified FTO as a potential non-hypoxia inducible factor (HIF) classical substrate of VHL, highlighted the critical role of FTO in regulating m6A levels in ccRCC progression, and identified the CK2-FTO-EGR1-P53 regulatory axis as a potential target for the treatment of VHL-deficient ccRCC.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_00:20:13.735.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	国邦 李
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-02 07:51:52	ID requested
⏵ 1	2025-08-08 00:20:14	announced

Dataset with its publication pending

submitter keyword: CK2, m6A,VHL, FTO, ccRCC

Bo Li
contact affiliation	Department of Urology, Guangdong Provincial People's Hospital
contact email	liguobang@gdph.org.cn
lab head
国邦 李
contact affiliation	Guangdong Provincial People's Hospital
contact email	ligb020@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053566
     1. Label: PRIDE project
     2. Name: VHL acts as an adaptor to promote the phosphorylation of FTO by CK2 to suppress clear cell renal cell carcinoma