PXD025033
PXD025033 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A novel regulatory mechanism of U2 spliceosome proteostasis that controls the transcriptome and therapy response in cancer |
| Description | Aberrant splicing is an important cause of cancer, and the production of noncanonical, cancer-specific, mRNA transcripts associates with transformation. Studies have focused on characterizing the effect of spliceosome mutations on disease progression. Here, we have uncovered a novel mode of regulation of the U2 complex component SF3B1 in leukemia via lysosomal degradation. Elevated levels of SF3B1 protein control splicing and active transcription via direct interaction with the general transcriptional machinery and are critical for leukemia growth due to the control of cell cycle and DNA damage response-related transcripts, such as the serine/threonine kinase CHEK2. We further exploited these findings to show that clinically-used SF3B1 inhibitors synergize with transcriptional inhibitors, CHEK2 inhibitors and chemotherapy drugs to block leukemia growth. Our study provides the proof-of-principle for post-translational regulation of the splicing machinery via the lysosome and associated splicing-dependent and -independent roles of the U2 complex in cancer, that can be exploited for therapeutic purposes. |
| HostingRepository | MassIVE |
| AnnounceDate | 2022-02-19 |
| AnnouncementXML | Submission_2022-02-19_12:35:25.854.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Cho Byoung-Kyu |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-03-26 13:34:50 | ID requested | |
| ⏵ 1 | 2022-02-19 12:35:26 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Human, T-ALL, LFQ |
Contact List
| Young Ah Goo | |
|---|---|
| contact affiliation | Northwestern University |
| contact email | young.goo@northwestern.edu |
| lab head | |
| Cho Byoung-Kyu | |
| contact affiliation | Northwestern University |
| contact email | byoungkyu.cho@northwestern.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/MSV000087113/ |
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