PXD047661-1
PXD047661 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Proteostasis perturbation of N-Myc by HSP70 inhibition improves treatment in neuroendocrine prostate cancer |
| Description | N-Myc is a key driver of neuroendocrine tumors, such as neuroblastoma and neuroendocrine prostate cancer. However, N-Myc is considered undruggable because it lacks clear binding sites for small molecules. One potential way to circumvent this challenge is to identify and target the protein homeostasis proteostasis systems that maintain N-Myc levels. Here we developed a novel spontaneously indefinite prostate cancer cell line UCDCaP and its paired castration-resistant line UCDCaP-CR, which exhibits neural lineage plasticity and high levels of N-Myc protein expression. Through rapid immunoprecipitation mass spectrometry assay, we revealed that heat shock protein 70, HSP70 is a top partner for N-Myc. HSP70 is known to function in protein folding and it also coordinates with the E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1, STUB1, to regulate oncoprotein degradation. We find that HSP70 binds a conserved SELILKR motif and prevents the access of STUB1 on N-Myc possibly through steric hindrance. When HSP70 dwell time on N-Myc is increased by the conformational change of HSP70, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites of the bHLH-LZ domain and form the poly ubiquitination chains linked by the K11 and K63 sites. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-07-05 |
| AnnouncementXML | Submission_2024-07-05_16:36:20.251.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | gabriela grigorean |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | CarbamidomethylDTT; Oxidation |
| Instrument | timsTOF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-12-08 11:14:14 | ID requested | |
| ⏵ 1 | 2024-07-05 16:36:20 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Prostate cancer, Neuroendocrine, Proteostasis, N-Myc, HSP70, STUB1, Ubiquitination, Therapy |
Contact List
| Chengfei Liu | |
|---|---|
| contact affiliation | University Of California, Davis |
| contact email | cffliu@ucdavis.edu |
| lab head | |
| gabriela grigorean | |
| contact affiliation | ucd |
| contact email | ggrigorean@ucdavis.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v06/MSV000093611/ |
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