PXD061128

PXD061128 is an original dataset announced via ProteomeXchange.

Title	IAP-binding intrabodies for concurrent degradation of proto-oncogenes and toggling cell death modalities
Description	Single domain antibodies or antibody mimetics, such as monobodies, can be engineered to degrade undruggable targets via fusion to ubiquitin E3 ligases. In this study we developed multi-targeting biodegrader intrabodies by harnessing an inhibitor of apoptosis (IAP) E3 ligase RING domain, or the IAP-binding motif from SMAC/DIABLO. When fused with monobodies targeting the necroptotic death effector MLKL, IAP-binding intrabodies simultaneously targeted MLKL and IAPs for proteasomal degradation, thereby blocking necroptosis while sensitising cells to apoptosis. The potent degradative capacity of the IAP RING was demonstrated via its fusion to distinct antibody mimetics, with those targeting RAS enabling IAP and RAS proto-oncogenes to be concurrently eliminated. Quantitative proteomics identified that the anti-cancer potential of select IAP-binding intrabodies was due to their removal of the chromatin remodelling BAF complex. Consequently, we show that cancer cells exhibited IAP and BAF co-dependencies, with IAP RING intrabodies prolonging animal survival in an orthotopic breast cancer model. This work positions IAP-binding intrabodies as a novel class of biodegraders, with their multi-targeting capacity enabling the toggling of cell death modalities and eradication of cancer-drivers.
HostingRepository	PRIDE
AnnounceDate	2026-03-03
AnnouncementXML	Submission_2026-03-02_18:48:33.702.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Tanzer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-24 03:54:06	ID requested
⏵ 1	2026-03-02 18:48:34	announced

Dataset with its publication pending

submitter keyword: intrabody, cancer,IAP protein, drugs, TNF, BAF, biodegrader, cIAP1, XIAP, bioPROTAC, smac mimetic, RING, PROTAC, SWI/SNF, intracellular antibody, E3 ligase

James Vince
contact affiliation	Walter and Elisa Hall Institute of Medical Research Inflammation Division
contact email	vince@wehi.edu.au
lab head
Maria Tanzer
contact affiliation	Walter and Eliza Hall Institute
contact email	tanzer@wehi.edu.au
dataset submitter

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/2026/03/PXD061128

PRIDE project URI

• PRIDE
  1. PXD061128
     1. Label: PRIDE project
     2. Name: IAP-binding intrabodies for concurrent degradation of proto-oncogenes and toggling cell death modalities