RGD Reference Report - Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects.

Authors: Dooley, S  Said, HM  Gressner, AM  Floege, J  En-Nia, A  Mertens, PR 
Citation: Dooley S, etal., J Biol Chem. 2006 Jan 20;281(3):1784-95. Epub 2005 Nov 8.
RGD ID: 1580627
Pubmed: PMID:16278212   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M510215200   (Journal Full-text)

Y-box protein-1 (YB-1) is a known negative regulator of collagen (Col) expression by two different mechanisms, acting directly through binding to an interferon-gamma response element within the col1A2 promoter and/or by physically interacting with p300/Smad3, thereby abrogating the stimulatory effect of transforming growth factor-beta (TGF-beta). Here, we report that YB-1 activation via the Jak1 signaling pathway is required and sufficient to confer interferon-gamma-dependent activation of the smad7 gene. By binding to a bona fide recognition site within the smad7 promoter, YB-1 up-regulates smad7 transcription, which was additively enhanced by autoinhibitory TGF-beta signaling. Importantly, the anti-TGF-beta effect was not only supplied by induced Smad7 expression but was recapitulated in the context of the col1A2 promoter, where YB-1 overexpression abolished the trans-stimulatory TGF-beta effect in a dominant fashion. In conclusion, YB-1 is the main target of interferon-gamma signaling via Jak1 that exerts antifibrotic action by both interference with TGF-beta signaling and direct down-regulation of collagen expression.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ybx1Ratsequence-specific DNA binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ybx1  (Y box binding protein 1)


Additional Information