Document Detail

Ebp1 isoforms distinctively regulate cell survival and differentiation.
MedLine Citation:
PMID:  16832058     Owner:  NLM     Status:  MEDLINE    
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.
Zhixue Liu; Jee-Yin Ahn; Xia Liu; Keqiang Ye
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-07-10
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-19     Completed Date:  2006-08-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10917-22     Citation Subset:  IM    
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
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MeSH Terms
Active Transport, Cell Nucleus
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Base Sequence
Cell Differentiation*
Cell Line
Cell Nucleolus
Cell Survival
Conserved Sequence
Molecular Sequence Data
Molecular Weight
Protein Binding
Protein Isoforms / genetics,  metabolism
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptor, erbB-3 / metabolism
Sequence Alignment
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Ebp1 protein, rat; 0/Protein Isoforms; EC, erbB-3; EC Proteins c-akt; EC Kinase C

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