PMID- 21852538
OWN - NLM
STAT- MEDLINE
DCOM- 20120228
LR  - 20161125
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 25
IP  - 12
DP  - 2011 Dec
TI  - Calsenilin regulates presenilin 1/gamma-secretase-mediated N-cadherin epsilon-cleavage and 
      beta-catenin signaling.
PG  - 4174-83
LID - 10.1096/fj.11-185926 [doi]
AB  - Presenilin 1 (PS1) is a component of the gamma-secretase complex that cleaves a 
      variety of type I membrane proteins, including the beta-amyloid precursor protein 
      (beta-APP), Notch, and neuronal (N)- and epithelial (E)-cadherins. N-cadherin is an 
      essential adhesion molecule that forms a complex with, and is cleaved by, 
      PS1/gamma-secretase and beta-catenin in the plasma membrane. The purpose of this study 
      was to determine whether calsenilin, a presenilin-interacting protein, has a 
      functional role in PS1/gamma-secretase-mediated N-cadherin epsilon-cleavage using Western 
      blot analysis, RT-PCR, immunoprecipitation, subcellular fractionation, 
      biotinylation, and a luciferase reporter assay in SH-SY5Y neuroblastoma cells. 
      Here, we demonstrate that the expression of calsenilin leads to a disruption of 
      PS1/gamma-secretase-mediated epsilon-cleavage of N-cadherin, which results in the 
      significant accumulation of N-cadherin C-terminal fragment 1 (Ncad/CTF1), the 
      reduction of cytoplasmic Ncad/CTF2 release, and a deceleration of PS1-CTF 
      delivery to the cell surface. Interestingly, we also found that the expression of 
      calsenilin is associated with the redistribution of beta-catenin from the cell 
      surface to a cytoplasmic pool, as well as with the negative regulation of genes 
      that are targets of T-cell factor/beta-catenin nuclear signaling. Taken together, 
      our findings suggest that calsenilin is a novel negative regulator of N-cadherin 
      processing that plays an important role in beta-catenin signaling.
FAU - Jang, Changhwan
AU  - Jang C
AD  - Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, 
      Dongan-gu, Anyang, Gyeonggi-do 431-060, Republic of Korea.
FAU - Choi, Jin-Kyu
AU  - Choi JK
FAU - Na, Yeo-Jung
AU  - Na YJ
FAU - Jang, Byungki
AU  - Jang B
FAU - Wasco, Wilma
AU  - Wasco W
FAU - Buxbaum, Joseph D
AU  - Buxbaum JD
FAU - Kim, Yong-Sun
AU  - Kim YS
FAU - Choi, Eun-Kyoung
AU  - Choi EK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110818
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antigens, CD)
RN  - 0 (CDH2 protein, human)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (KCNIP3 protein, human)
RN  - 0 (Kv Channel-Interacting Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 0 (Repressor Proteins)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Amyloid Precursor Protein Secretases/*metabolism
MH  - Antigens, CD/chemistry/*metabolism
MH  - Cadherins/chemistry/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Humans
MH  - Kv Channel-Interacting Proteins/genetics/*metabolism
MH  - Models, Neurological
MH  - Neuroblastoma/genetics/metabolism
MH  - Presenilin-1/*metabolism
MH  - Protein Structure, Tertiary
MH  - Proteolysis
MH  - Repressor Proteins/genetics/*metabolism
MH  - Signal Transduction
MH  - beta Catenin/genetics/*metabolism
EDAT- 2011/08/20 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/08/20 06:00
PHST- 2011/08/20 06:00 [entrez]
PHST- 2011/08/20 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - fj.11-185926 [pii]
AID - 10.1096/fj.11-185926 [doi]
PST - ppublish
SO  - FASEB J. 2011 Dec;25(12):4174-83. doi: 10.1096/fj.11-185926. Epub 2011 Aug 18.