RGD Reference Report - A thrombospondin-dependent pathway for a protective ER stress response. - Rat Genome Database

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A thrombospondin-dependent pathway for a protective ER stress response.

Authors: Lynch, JM  Maillet, M  Vanhoutte, D  Schloemer, A  Sargent, MA  Blair, NS  Lynch, KA  Okada, T  Aronow, BJ  Osinska, H  Prywes, R  Lorenz, JN  Mori, K  Lawler, J  Robbins, J  Molkentin, JD 
Citation: Lynch JM, etal., Cell. 2012 Jun 8;149(6):1257-68. doi: 10.1016/j.cell.2012.03.050.
RGD ID: 8554640
Pubmed: PMID:22682248   (View Abstract at PubMed)
PMCID: PMC3372931   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2012.03.050   (Journal Full-text)

Thrombospondin (Thbs) proteins are induced in sites of tissue damage or active remodeling. The endoplasmic reticulum (ER) stress response is also prominently induced with disease where it regulates protein production and resolution of misfolded proteins. Here we describe a function for Thbs as ER-resident effectors of an adaptive ER stress response. Thbs4 cardiac-specific transgenic mice were protected from myocardial injury, whereas Thbs4(-/-) mice were sensitized to cardiac maladaptation. Thbs induction produced a unique profile of adaptive ER stress response factors and expansion of the ER and downstream vesicles. Thbs bind the ER lumenal domain of activating transcription factor 6alpha (Atf6alpha) to promote its nuclear shuttling. Thbs4(-/-) mice showed blunted activation of Atf6alpha and other ER stress-response factors with injury, and Thbs4-mediated protection was lost upon Atf6alpha deletion. Hence, Thbs can function inside the cell during disease remodeling to augment ER function and protect through a mechanism involving regulation of Atf6alpha.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Atf6Ratnucleus located_inIDA PMID:22682248UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Atf6  (activating transcription factor 6)


Additional Information