Document Detail

HER2 stabilizes survivin while concomitantly down-regulating survivin gene transcription by suppressing Notch cleavage.
MedLine Citation:
PMID:  23323858     Owner:  NLM     Status:  Publisher    
In breast cancer, the HER2 receptor tyrosine kinase is associated with extremely poor prognosis and survival. Notch signaling has a key role in cell-fate decision especially in cancer-initiating cells. The Notch intracellular domain produced by Notch cleavage is translocated to the nucleus where it activates transcription of target genes. To determine the combinatory effect of HER2 and Notch signaling in breast cancer, we investigated the effect of HER2 on Notch-induced cellular phenomena. We found the down-regulation of Notch-dependent transcriptional activity by HER2 overexpression. Also, the HER2/ERK signal pathway down-regulated the activity of g-secretase. When we examined the protein level of Notch target genes in HER2-overexpressing cells, we observed that the level of survivin, downstream of Notch, increased in HER2 cells. We found that activation of ERK resulted in a decrease of XAF1 which reduced the formation of XIAP-XAF1 E3 ligase complex to ubiquitinate survivin. In addition, T34 of survivin was shown to be the most important residue in determining survivin stability upon phosphorylation after HER2/Akt/CDK1-cyclin B1 signaling. Our results show the combinatorial effects of HER2 and Notch during breast oncogenesis.
Ji-Hyun Ju; Wonseok Yang; Sunhwa Oh; Keesoo Nam; Kyung-Min Lee; Dong-Young Noh; Incheol Shin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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