PXD057237-2

PXD057237 is an original dataset announced via ProteomeXchange.

Title	REGγ is essential to maintain bone homeostasis by degrading TRAF6, preventing osteoporosis
Description	Primary osteoporosis, manifesting as decreased bone mass and increased bone fragility, is a “silent disease” that is often ignored until a bone breaks. Accordingly, it is urgent to develop reliable biomarkers and novel therapeutic strategies for osteoporosis treatment. Here, we identified REGγ as a potential biomarker of osteoporotic populations through proteomics analysis. Next, we demonstrated that REGγ deficiency increased osteoclast activity and triggered bone mass loss in REGγ knockout (KO) and bone marrow-derive macrophage (BMM)-conditional REGγ KO mice. However, the osteoclast activity decreased in BMM-conditional REGγ overexpression mice. Mechanistically, we defined that REGγ-20S proteasome directly degraded TRAF6 to inhibit bone absorption in a ubiquitin-independent pathway. More importantly, BMM-conditional Traf6 KO with REGγ KO mice could “rescue” the osteoporosis phenotypes. Based on NIP30 (a REGγ “inhibitor”) dephosphorylation by CKII inhibition activated the ubiquitin-independent degradation of TRAF6, we selected TTP22, an inhibitor of CKII, and defined that TTP22 could alleviate osteoporosis in vitro and in vivo. Overall, our study reveals a unique function of NIP30/REGγ/TRAF6 axis in osteoporosis and provides a potential therapeutic drug TTP22 for osteoporosis.
HostingRepository	iProX
AnnounceDate	2024-10-27
AnnouncementXML	Submission_2024-12-25_19:19:42.212.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hui Chen
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-27 21:06:46	ID requested
1	2024-10-27 21:07:13	announced
⏵ 2	2024-12-25 19:19:43	announced	2024-12-26: Add Publication.

Du Y, Chen H, Zhou L, Guo Q, Gong S, Feng S, Guan Q, Shi P, Lv T, Guo Y, Yang C, Sun P, Li K, Xu S, Li L, is essential to maintain bone homeostasis by degrading TRAF6, preventing osteoporosis. Proc Natl Acad Sci U S A, 121(47):e2405265121(2024) [pubmed]

submitter keyword: ubiquitin-independent degradation, REGγ, TRAF6, NIP30, osteoporosis

Lei Li
contact affiliation	East China Normal University
contact email	lli@bio.ecnu.edu.cn
lab head
Hui Chen
contact affiliation	East China Normal University
contact email	chuisunshine@126.com
dataset submitter

iProX dataset URI