PXD045686

PXD045686 is an original dataset announced via ProteomeXchange.

Title	Targeting neddylation is a novel therapeutic strategy for lupus by reconstructing double negative T cell homeostasis
Description	Systemic lupus erythematosus (SLE) is an autoimmune disorder with systemic inflammation, autoantibody accumulation and organ damage. The abnormalities of double-negative (DN) T cells are considered as an important commander of SLE. Neddylation, an important type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE remains largely unexplored. Here, we reported that neddylation inactivation with MLN4924 or genetic abrogation of Ube2m in T cells prevented SLE development for decreased DN T cell accumulation. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells for Fas mutation. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim interrupted the improvement of DN T cell apoptosis and the consequential relieved lupus symptoms for Ube2m KO. Our findings identified that neddylation inactivation promoted Bim-mediated apoptosis of DN T cells and prevented lupus progress. Clinically, we also found the percentages of DN T cells were improved accompanied with reduced apoptosis of DN T cells in SLE patients. Moreover, the neddylation of Cullin1 was higher while Bim level was decreased in SLE patients compared with healthy control. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Together, these findings provide the first evidence of the neddylation role in lupus development, suggesting a novel therapeutic strategy for lupus.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_07:28:56.464.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yun Zhang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-25 23:14:44	ID requested
⏵ 1	2024-01-26 07:28:57	announced

10.1038/s41392-023-01709-9;

Zhang Y, Du L, Wang C, Jiang Z, Duan Q, Li Y, Xie Z, He Z, Sun Y, Huang L, Lu L, Wen C, Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis. Signal Transduct Target Ther, 9(1):18(2024) [pubmed]

submitter keyword: Neddylation

Ube2m

Systemic lupus erythematosus (SLE)

Bim

Double negative T cells (DN T cells)

Apoptosis

Yun Zhang
contact affiliation	Zhejiang Chinese Medical University,Hangzhou,China
contact email	zhangyun@zcmu.edu.cn
lab head
Yun Zhang
contact affiliation	Zhejiang Chinese Medical University
contact email	zhangyun@zcmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045686
     1. Label: PRIDE project
     2. Name: Targeting neddylation is a novel therapeutic strategy for lupus by reconstructing double negative T cell homeostasis