PXD055145

PXD055145 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-23 10:31:16	ID requested
⏵ 1	2025-05-07 01:32:37	announced

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]

submitter keyword: SPTBN1 aldehydes 4-hydroxynonenal

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

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PRIDE project URI

• PRIDE
  1. PXD055145
     1. Label: PRIDE project
     2. Name: Aldehydes alter TGF-b signaling and induce obesity and cancer