PXD059464-1

PXD059464 is an original dataset announced via ProteomeXchange.

Title	Nuclear-localized HKDC1 promotes hepatocellular carcinoma through phosphorylating RBBP5 to upregulate H3K4me3
Description	Metabolic enzymes play significant roles in the pathogenesis of various cancers through both canonical and noncanonical functions. Hexokinase domain-containing protein 1 (HKDC1) functions beyond glucose metabolism, but its underlying mechanisms in tumorigenesis are not fully understood. Here, we demonstrate that nuclear-localized HKDC1 acts as a protein kinase to promote hepatocellular carcinoma (HCC) cell proliferation. Mechanistically, HKDC1 phosphorylates RB binding protein 5 (RBBP5) at Ser497, which is crucial for MLL1 complex assembly and subsequent H3K4me3 modification. This leads to the transcriptional activation of mitosis-related genes, thereby driving cell cycle progression and proliferation. Notably, targeting HKDC1’s protein kinase activity, but not its hexokinase activity, blocks RBBP5 phosphorylation and suppresses tumor growth. Clinical analysis further reveals that RBBP5 phosphorylation positively correlates with HKDC1 levels and poor HCC prognosis. These findings highlight the protein kinase function of HKDC1 in the activation of H3K4me3, gene expression, and HCC progression.
HostingRepository	PRIDE
AnnounceDate	2025-01-07
AnnouncementXML	Submission_2025-01-06_20:25:05.405.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Ye
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-06 07:39:06	ID requested
⏵ 1	2025-01-06 20:25:05	announced

Dataset with its publication pending

submitter keyword: Human, HCC, IP-MS

Huafeng Zhang
contact affiliation	University of Science and Technology of China
contact email	hzhang22@ustc.edu.cn
lab head
Ling Ye
contact affiliation	University of Science and Technology of China
contact email	yeling10@mail.ustc.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059464
     1. Label: PRIDE project
     2. Name: Nuclear-localized HKDC1 promotes hepatocellular carcinoma through phosphorylating RBBP5 to upregulate H3K4me3