PXD055145 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Aldehydes alter TGF-b signaling and induce obesity and cancer |
Description | Obesity and fatty liver diseases—metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)—affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2KO and Aldh2KO/Sptbn1 KO/WT mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor b (TGF-b) signaling through 4-HNE modification of the SMAD3 adaptor SPTBN1 (b2-spectrin) to proQ8 fibrotic and pro-oncogenic phenotypes, which is restored to normal with small interfering RNA (siRNA) to SPTBN1. Significantly, therapeutic inhibition of SPTBN1 blocks MASH and fibrosis in a human model. This study identifies SPTBN1 as a critical regulator of the functional phenotype of toxic aldehyde-induced MASH and a potential therapeutic Q2 target. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-07_01:32:36.795.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Paolo Cifani |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 4-hydroxynonenal adduct |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-08-23 10:31:16 | ID requested | |
⏵ 1 | 2025-05-07 01:32:37 | announced | |
Publication List
10.1016/j.celrep.2024.114676; |
Yang X, Bhowmick K, Rao S, Xiang X, Ohshiro K, Amdur RL, Hassan MI, Mohammad T, Crandall K, Cifani P, Shetty K, Lyons SK, Merrill JR, Vegesna AK, John S, Latham PS, Crawford JM, Mishra B, Dasarathy S, Wang XW, Yu H, Wang Z, Huang H, Krainer AR, Mishra L, signaling and induce obesity and cancer. Cell Rep, 43(9):114676(2024) [pubmed] |
Keyword List
submitter keyword: SPTBN1 aldehydes 4-hydroxynonenal |
Contact List
Paolo Cifani |
contact affiliation | COld Spring Harbor Laboratory |
contact email | cshl.mass.spec@gmail.com |
lab head | |
Paolo Cifani |
contact affiliation | Cold Spring Harbor Laboratory |
contact email | cshl.mass.spec@gmail.com |
dataset submitter | |
Full Dataset Link List
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/2025/05/PXD055145 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD055145
- Label: PRIDE project
- Name: Aldehydes alter TGF-b signaling and induce obesity and cancer