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PXD074677
PXD074677 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Lactate controls activation of CDK1 by neddylation to promote mitosis transition in hypoxia |
| Description | The G2/M transition is a highly energy-demanding processes in cell division, during which glycolysis-derived lactate metabolism provides a rapid energy supply. Lactate accumulation and the resulting hypoxic microenvironment have been implicated in tumor recurrence and therapy resistance. Here, we show that lactate markedly accumulates during the G2/M phase. This elevated lactate induces a high level of lactylation, which is associated with poor prognosis in patients with recurrent hepatocellular carcinoma (HCC). Mechanistically, we demonstrate that lactate-driven lactylation enhances the protein stability of the ubiquitin-conjugating enzyme E2 (UBE2M). UBE2M-mediated neddylation of CDK1 at the K20 site promotes the assembly of the CDK1-Cyclin B complex, thereby increasing CDK1 kinase activity to accelate G2/M transition. Moreover, neddylation-active CDK1 phosphorylates lactate dehydrogenase A (LDHA) at Thr74with lactate accumulation during the G2/M phase, a previously unrecognized modification that facilitates NADH regeneration and boosts lactate production. Consistently, mutation of the CDK1 neddylation site Lys20 attenuates LDHA phosphorylation and lactate generation. Finally, we identify theaflavin was a potent inhibitor of CDK1 neddylation that effectively sensitizes HCC to therapy. Collectively, our findings uncover a metabolic circuit in which neddylation couples with lactylation to rapidly meet energetic demands upon mitotic entry under tumor hypoxic conditions, suggesting a potential therapeutic strategy for cancer treatment. |
| HostingRepository | iProX |
| AnnounceDate | 2026-02-12 |
| AnnouncementXML | Submission_2026-02-20_02:49:11.758.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Yaxin Shang |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-02-20 02:47:06 | ID requested | |
| ⏵ 1 | 2026-02-20 02:49:12 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: CDK1, Neddylation, Lactate, UBE2M |
Contact List
| Ping Xie | |
|---|---|
| contact affiliation | Capital Medical University |
| contact email | xpxp922@163.com |
| lab head | |
| Yaxin Shang | |
| contact affiliation | Capital Medical University |
| contact email | syxhb97@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
