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PXD055145

PXD055145 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAldehydes alter TGF-b signaling and induce obesity and cancer
DescriptionObesity 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.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_01:32:36.795.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPaolo Cifani
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList4-hydroxynonenal adduct
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-08-23 10:31:16ID requested
12025-05-07 01:32:37announced
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 affiliationCOld Spring Harbor Laboratory
contact emailcshl.mass.spec@gmail.com
lab head
Paolo Cifani
contact affiliationCold Spring Harbor Laboratory
contact emailcshl.mass.spec@gmail.com
dataset submitter
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Dataset FTP location
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