PXD073992

PXD073992 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-03 06:17:20	ID requested
⏵ 1	2026-09-07 04:20:10	announced

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]

submitter keyword: Deslanoside, ATO, Targeted protein degradation,NPM-ALK+ ALCL, STUB1, Combination therapy

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

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PRIDE project URI

• PRIDE
  1. PXD073992
     1. Label: PRIDE project
     2. Name: Arsenic Trioxide Acts as a Molecular Glue to Promote STUB1-Mediated NPM-ALK Degradation in ALK⁺ ALCL