PMID- 23323858
OWN - NLM
STAT- MEDLINE
DCOM- 20130502
LR  - 20201209
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 451
IP  - 1
DP  - 2013 Apr 1
TI  - HER2 stabilizes survivin while concomitantly down-regulating survivin gene 
      transcription by suppressing Notch cleavage.
PG  - 123-34
LID - 10.1042/BJ20121716 [doi]
AB  - In breast cancer, the HER2 (human epidermal growth factor receptor 2) receptor 
      tyrosine kinase is associated with extremely poor prognosis and survival. Notch 
      signalling has a key role in cell-fate decisions, 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 signalling 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 (extracellular-signal-regulated kinase) signal 
      pathway down-regulated the activity of gamma-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 in XAF1 [XIAP (X-linked inhibitor of 
      apoptosis)-associated factor 1] which reduced the formation of the XIAP-XAF1 E3 
      ligase complex to ubiquitinate survivin. In addition, Thr(34) of survivin was 
      shown to be the most important residue in determining survivin stability upon 
      phosphorylation after HER2/Akt/CDK1 (cyclin-dependent kinase 1)-cyclin B1 
      signalling. The results of the present study show the combinatorial effects of 
      HER2 and Notch during breast oncogenesis.
FAU - Ju, Ji-hyun
AU  - Ju JH
AD  - Department of Life Science, Hanyang University, Seoul 133-791, Korea.
FAU - Yang, Wonseok
AU  - Yang W
FAU - Oh, Sunhwa
AU  - Oh S
FAU - Nam, KeeSoo
AU  - Nam K
FAU - Lee, Kyung-min
AU  - Lee KM
FAU - Noh, Dong-young
AU  - Noh DY
FAU - Shin, Incheol
AU  - Shin I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (Survivin)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XAF1 protein, human)
RN  - 0 (XIAP protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Apoptosis Regulatory Proteins
MH  - Breast Neoplasms/genetics/*metabolism
MH  - CDC2 Protein Kinase/genetics/metabolism
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Down-Regulation/genetics
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - HeLa Cells
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/*biosynthesis/genetics
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - *MAP Kinase Signaling System
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Protein Stability
MH  - *Proteolysis
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Receptors, Notch/chemistry/*metabolism
MH  - Survivin
MH  - *Transcription, Genetic
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
MH  - Ubiquitination/genetics
MH  - X-Linked Inhibitor of Apoptosis Protein/genetics/metabolism
EDAT- 2013/01/18 06:00
MHDA- 2013/05/03 06:00
CRDT- 2013/01/18 06:00
PHST- 2013/01/18 06:00 [entrez]
PHST- 2013/01/18 06:00 [pubmed]
PHST- 2013/05/03 06:00 [medline]
AID - BJ20121716 [pii]
AID - 10.1042/BJ20121716 [doi]
PST - ppublish
SO  - Biochem J. 2013 Apr 1;451(1):123-34. doi: 10.1042/BJ20121716.