PXD044895-2

PXD044895 is an original dataset announced via ProteomeXchange.

Title	TRIM55 promotes noncanonical NF-kB signaling and B-cell-mediated immune responses by coordinating p100 ubiquitination and processing
Description	The ubiquitination-dependent processing of NF-B2 (also known as p100) is a critical step in the activation of the noncanonical NF-B pathway. We investigated the molecular mechanisms regulating this process and showed that TRIM55 was the ubiquitin E3 ligase that mediated the ubiquitination of p100 and coordinated its processing. TRIM55 deficiency impaired noncanonical NF-B activation and B-cell function. Mice with a B cell-specific Trim55 deficiency exhibited reduced germinal center formation and antibody production. In addition, our data indicated a critical role of TRIM55 in the pathogenesis of lupus-like autoimmunological disorders, suggesting B-cell intrinsic functions of TRIM55 in humoral immune responses and autoimmunity. Mechanistically, the ubiquitination of p100 mediated by TRIM55 was crucial for p100 processing by VCP, an ATPase that mediates ubiquitin-dependent protein degradation by the proteasome. Furthermore, we found that TRIM55 facilitated the interaction between TRIM21 and VCP as well as TRIM21-mediated K63-ubiquitination of VCP, both of which were indispensable for the formation of the VCP-UFD1-NPL4 complex and p100 processing. Collectively, our results revealed a mechanism by which TRIM55 fine-tunes p100 processing and regulates B-cell-dependent immune responses in vivo, highlighting TRIM55 as a potential therapeutic target for lupus-like disease.
HostingRepository	iProX
AnnounceDate	2023-08-28
AnnouncementXML	Submission_2024-04-07_19:29:50.284.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanqiu Gong
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-27 20:37:35	ID requested
1	2023-08-27 20:37:52	announced
⏵ 2	2024-04-07 19:29:51	announced	2024-04-08: Update information.

Lin L, Yu H, Li L, Yang W, Chen X, Gong Y, Lei Q, Li Z, Zhou Z, Dai L, Zhang H, Hu H, B signaling and B cell-mediated immune responses by coordinating p100 ubiquitination and processing. Sci Signal, 16(806):eabn5410(2023) [pubmed]

submitter keyword: TRIM55, noncanonical NF-kB, p100 ubiquitination

Lunzhi Dai
contact affiliation	Sichuan University
contact email	lunzhi.dai@scu.edu.cn
lab head
Yanqiu Gong
contact affiliation	Sichuan University
contact email	niqiu.er@163.com
dataset submitter

iProX dataset URI