PXD068961

PXD068961 is an original dataset announced via ProteomeXchange.

Title	The crosstalk between CRL5 and APC/C E3 ligases regulates metastasis and chemo-sensitivity of cancer cells
Description	Cullin-RING ligases (CRLs) and the anaphase-promoting complex/cyclosome (APC/C) are two major multi-subunit ubiquitin ligases essential for protein homeostasis. The underlying mechanism and biological consequence of their crosstalk remain elusive. Here, we employed tandem affinity purification followed by LC-MS/MS and identified APC11—the RING subunit of APC/C—as a bona fide binding partner of CUL5, the scaffold of CRL5. On one hand, APC11 interacts with CUL5 and inhibits its neddylation. Consequently, APC11 knockdown enhances CUL5 neddylation by promoting its interaction with the neddylation E2 UBE2F. This leads to the degradation of SOCS3, a substrate receptor of CRL5, and the subsequent accumulation of its substrate, integrin Integrin β1, ultimately promoting cancer metastasis. On the other hand, CUL5-APC11 binding stabilizes APC11 by facilitating its atypical K27/K29/K33-linked polyubiquitylation at Lys83, a process catalyzed by ITCH E3 ligase. CUL5 loss delays mitotic exit, induces aneuploidy, and sensitizes cancer cells to the microtubule-targeting drug paclitaxel by destabilizing APC11. Collectively, our study revealed a new cross-talk between CUL5 and APC11 of two major E3 ligases, and targeting this cross-talk could provide a new strategy for blocking metastasis and triggering chemo-sensitization.
HostingRepository	PRIDE
AnnounceDate	2026-01-23
AnnouncementXML	Submission_2026-01-23_01:19:45.977.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Danrui Cui
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-29 05:19:30	ID requested
⏵ 1	2026-01-23 01:19:46	announced

10.1002/advs.202512652;

Cui D, Qu R, Li T, Wang L, Chen X, Shao S, Liang X, Xu J, Sun Y, Xiong X, Zhao Y, The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells. Adv Sci (Weinh), 13(3):e12652(2026) [pubmed]

submitter keyword: CUL5

APC11

neddylation

metastasis

chemo-sensitivity

Yongchao Zhao
contact affiliation	Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine
contact email	yongchao@zju.edu.cn
lab head
Danrui Cui
contact affiliation	Zhejiang University School of Medicine
contact email	cuidanrui@zju.edu.cn
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/2026/01/PXD068961

PRIDE project URI

• PRIDE
  1. PXD068961
     1. Label: PRIDE project
     2. Name: The crosstalk between CRL5 and APC/C E3 ligases regulates metastasis and chemo-sensitivity of cancer cells