PXD073992 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Arsenic Trioxide Acts as a Molecular Glue to Promote STUB1-Mediated NPM-ALK Degradation in ALK⁺ ALCL |
| Description | The NPM-ALK fusion constitutively activates ALK tyrosine kinase, driving oncogenesis in anaplastic large cell lymphoma (ALCL). Although arsenic trioxide (ATO) exhibits therapeutic potential in NPM-ALK⁺ ALCL by inhibiting proliferation and inducing apoptosis, its molecular mechanism remains unclear. Here, we used a combined approach of E3 ligase library screening, ATO chemical proteomics, and NPM-ALK immunoprecipitation–mass spectrometry to reveal that ATO regulates NPM–ALK stability via the E3 ligase STUB1. Comprehensive clinical data indicate that high STUB1 expression correlates with improved prognosis in NPM-ALK⁺ ALCL patients. In ALCL cells, both ATO treatment and STUB1 overexpression induce NPM-ALK degradation and suppress cell growth. Mechanistically, ATO functions as a molecular glue that stabilizes the ternary complex of STUB1 and NPM-ALK, promoting ubiquitination at K174 and subsequent proteasomal degradation. Furthermore, structural modeling identified C83 as an arsenic-bound site in STUB1 that modulates the STUB1-NPM-ALK interface, thereby enhancing their interaction and promoting ubiquitin-mediated degradation. Moreover, STUB1 overexpression or activation by Lanatoside C or Deslanoside markedly inhibits NPM‑ALK⁺ ALCL cells proliferation and synergizes with ATO in vitro and in vivo. These findings provide novel mechanistic insight into ATO’s action in NPM‑ALK⁺ ALCL and reveal new therapeutic strategies and clinical biomarkers for patient management. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-09-07 |
| AnnouncementXML | Submission_2026-09-07_04:20:09.410.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Wenbo Cheng |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | ubiquitinylated lysine |
| Instrument | Orbitrap Fusion Lumos; Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-02-03 06:17:20 | ID requested | |
| ⏵ 1 | 2026-09-07 04:20:10 | announced | |
Publication List
| 10.1186/s40164-026-00800-5; |
| Li G, Wang J, Ye S, Zhou L, Sun Y, Li B, Zhao Y, Ding Y, Zeng Y, Xue B, Wang G, Wang F, Luo X, Liang A, Weisberg EL, Zhang W, Lu W, Yang J, ALCL. Exp Hematol Oncol, 15(1):(2026) [pubmed] |
Keyword List
| submitter keyword: Deslanoside, ATO, Targeted protein degradation,NPM-ALK+ ALCL, STUB1, Combination therapy |
Contact List
| Jing Yang |
|---|
| contact affiliation | 1Department of Hematology, Tongji Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China |
| contact email | jingy@tongji.edu.cn |
| lab head | |
| Wenbo Cheng |
|---|
| contact affiliation | Shanghai Omicsspace Bioteh CO., LTD |
| contact email | wbcheng@omicsspace.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD073992
- Label: PRIDE project
- Name: Arsenic Trioxide Acts as a Molecular Glue to Promote STUB1-Mediated NPM-ALK Degradation in ALK⁺ ALCL
