RGD Reference Report - Ebp1 isoforms distinctively regulate cell survival and differentiation. - Rat Genome Database

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Ebp1 isoforms distinctively regulate cell survival and differentiation.

Authors: Liu, Z  Ahn, JY  Liu, X  Ye, K 
Citation: Liu Z, etal., Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10917-22. Epub 2006 Jul 10.
RGD ID: 10047374
Pubmed: PMID:16832058   (View Abstract at PubMed)
PMCID: PMC1544149   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0602923103   (Journal Full-text)

Ebp1, an ErbB3 receptor-binding protein, inhibits the proliferation and induces the differentiation of human cancer cells. Ebp1 binds nuclear Akt and prevents DNA fragmentation by inhibiting caspase-activated DNase. Here, we show that Ebp1 possesses two different isoforms, p48 and p42, which differentially mediate PC12 cell survival and differentiation. The longer-form p48 localizes in both the cytoplasm and the nucleus and suppresses apoptosis, whereas the shorter-form p42 predominantly resides in the cytoplasm and promotes cell differentiation. EGF strongly stimulates p42 to bind ErbB3, and the association depends on PKC-mediated phosphorylation of Ebp1. By contrast, p48 does not bind to ErbB3 regardless of EGF treatment. Overexpression of p48 provokes cell proliferation, which is inhibited by p42. Moreover, nerve growth factor elicits extensive sprouting in p42 stably transfected PC12 cells, whereas p48 cells reveal modest neurite outgrowth. Although mitogen-activated protein kinase cascade remains similar in both cells, Akt is more active in p48 cells than in p42 cells. Thus, Ebp1 might regulate cell survival and differentiation through two distinctive p48 and p42 isoforms.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process involved_inIDA 10047374PMID:16832058UniProt 
positive regulation of cell differentiation involved_inIDA 10047374PMID:16832058UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 10047374PMID:16832058UniProt 
nucleolus located_inIDA 10047374PMID:16832058UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q6AYD310047374PMID:16832058UniProt 
protein binding enablesIPIUniProtKB:P4719610047374PMID:16832058UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Pa2g4  (proliferation-associated 2G4)


Additional Information