PXD072306 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Degron-independent recruitment of KAT2A redefines the breadth of CRBN-based molecular-glue targets |
| Description | Lysine acetyltransferases (KATs) frequently cooperate with oncogenes such as c-Myc, estrogen receptor, and KMT2A-fusions to sustain malignant programs. Therapeutic targeting of KAT proteins has shown clinical efficacy, yet achieving homolog-selectivity for most KATs remains a major challenge. Here, by extending CRBN-based molecular glues beyond the canonical degron space, we develop a degrader of KAT2A exhibiting biochemical selectivity over all members of the KAT family. Cryo-EM structures reveal that CRBN engages KAT2A independent of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Optimized molecular glues demonstrate that selective KAT2A degradation leads to potent ablation of H3K9Ac, antiproliferative effects in AML cell lines, and in vivo efficacy in a patient-derived xenograft model. Overall, these findings establish KAT2A as a targetable vulnerability, laying the foundation for the development of KAT2A-degrading molecular glues to treat a wide range of malignancies. More generally, the unanticipated binding mode suggests that CRBN-based molecular glues may be limited only by the accessible chemical diversity. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-29 |
| AnnouncementXML | Submission_2026-08-29_13:28:38.879.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Eric Fischer |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | iodoacetamide derivatized residue |
| Instrument | timsTOF Ultra; timsTOF HT |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-12-22 12:49:32 | ID requested | |
| ⏵ 1 | 2026-08-29 13:28:39 | announced | |
Publication List
| 10.1126/science.aef5391; |
| Ojeda S, Wang M, Baek K, Bourgeois W, Sommerschield A, Yue H, Metivier RJ, Karagiannis P, Levitz TS, Xiong Y, Donovan KA, Armstrong SA, Fischer ES, Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues. Science, 393(6807):188-194(2026) [pubmed] |
Keyword List
| submitter keyword: Ubiquitin, kat2a, CRBN, molecular glue, Lysine acetyltransferases, protein degradation, E3 ligase, AML |
Contact List
| Eric Fischer |
|---|
| contact affiliation | Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA |
| contact email | eric_fischer@dfci.harvard.edu |
| lab head | |
| Eric Fischer |
|---|
| contact affiliation | Dana-Farber Cancer Institute |
| contact email | eric_fischer@dfci.harvard.edu |
| 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/2026/08/PXD072306 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD072306
- Label: PRIDE project
- Name: Degron-independent recruitment of KAT2A redefines the breadth of CRBN-based molecular-glue targets
