PXD049704
PXD049704 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis |
| Description | MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation. |
| HostingRepository | iProX |
| AnnounceDate | 2024-02-19 |
| AnnouncementXML | Submission_2024-04-14_23:46:02.266.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Zhenlei Zhang |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-02-19 19:30:15 | ID requested | |
| ⏵ 1 | 2024-04-14 23:46:02 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: TBX3, BRAF/MARK, Proteostatic reactivation |
Contact List
| Li Zhao | |
|---|---|
| contact affiliation | Tianjin Medical University |
| contact email | shzhaoli@tmu.edu.cn |
| lab head | |
| Zhenlei Zhang | |
| contact affiliation | Tianjin Medical University |
| contact email | zhangzhenlei0413@tmu.edu.cn |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
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