PXD030297
PXD030297 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Structural mechanism for inhibition of PP2A-B56 and oncogenicity by CIP2A |
| Description | Abstract The protein phosphatase 2A (PP2A) heterotrimer PP2A-B56 is a human tumor suppressor. However, the molecular mechanisms inhibiting PP2A-B56in cancer are poorly understood. Here, we report molecular level details and structural mechanism of PP2A-B56inhibition by an oncoprotein CIP2A. Upon direct binding to PP2A-B56 trimer, CIP2A replaces PP2A-A subunit and thereby hijacks both the B56 and the catalytic PP2Ac subunit to form a CIP2A-B56-PP2Ac pseudotrimer. Further, CIP2A competes with B56 substrate binding by blocking the LxxIxE-motif substrate binding pocket on B56. Relevant to oncogenic activity of CIP2A across human cancers, the N-terminal head domain-mediated interaction with B56 stabilizes CIP2A protein. Functionally, CRISPR/Cas9-mediated single amino acid mutagenesis of the head domain blunted MYC expression and MEK phosphorylation, and abrogated triple-negative breast cancer in vivo tumor growth. Collectively, we discover a unique multi-step “hijack and mute” mechanism of protein complex regulation inhibiting tumor suppressor PP2A-B56. Further, the results unfold single structural determinant for CIP2A´s oncogenic activity, potentially facilitating therapeutic modulation of CIP2A in cancer and other diseases. |
| HostingRepository | PRIDE |
| AnnounceDate | 2023-11-14 |
| AnnouncementXML | Submission_2023-11-14_08:39:26.320.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD030297 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Rita Derua |
| SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | LTQ Orbitrap Elite |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-12-10 02:42:06 | ID requested | |
| 1 | 2023-03-11 00:28:09 | announced | |
| ⏵ 2 | 2023-11-14 08:39:27 | announced | 2023-11-14: Updated project metadata. |
Publication List
| 10.6019/PXD030297; |
| Pavic K, Gupta N, Omella JD, Derua R, Aakula A, Huhtaniemi R, M, ä, ä, tt, ä JA, H, ö, fflin N, Okkeri J, Wang Z, Kauko O, Varjus R, Honkanen H, Abankwa D, K, ö, hn M, Hyt, ö, nen VP, Xu W, Nilsson J, Page R, Janssens V, Leitner A, Westermarck J, and oncogenicity by CIP2A. Nat Commun, 14(1):1143(2023) [pubmed] |
Keyword List
| submitter keyword: AP-MS, protein phosphatase,Mouse, oncogene, interactome |
Contact List
| Jukka Westermarck | |
|---|---|
| contact affiliation | Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland Institute of Biomedicine, University of Turku, 20520 Turku, Finland |
| contact email | jukka.westermarck@utu.fi |
| lab head | |
| Rita Derua | |
| contact affiliation | KU Leuven |
| contact email | rita.derua@kuleuven.be |
| dataset submitter | |
Full Dataset Link List
| 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://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD030297 |
| PRIDE project URI |
Repository Record List
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