PMID- 28782520
OWN - NLM
STAT- MEDLINE
DCOM- 20170925
LR  - 20171129
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 492
IP  - 1
DP  - 2017 Oct 7
TI  - Direct interaction of menin leads to ubiquitin-proteasomal degradation of 
      beta-catenin.
PG  - 128-134
LID - S0006-291X(17)31547-4 [pii]
LID - 10.1016/j.bbrc.2017.08.011 [doi]
AB  - Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor 
      suppressor and transcription regulator. Menin interacts with various proteins as 
      a scaffold protein and is proposed to play important roles in multiple 
      physiological and pathological processes by controlling gene expression, 
      proliferation, and apoptosis. The mechanisms underlying menin's suppression of 
      tumorigenesis are largely elusive. In this study, we showed that menin was 
      essential for the regulation of canonical Wnt/beta-catenin signaling in cultured 
      cells. The C-terminal domain of menin was able to directly interact with and 
      promote ubiquitin-mediated degradation of beta-catenin. We further revealed that 
      overexpression of menin down-regulated the transcriptional activity of beta-catenin 
      and target gene expression. Moreover, menin efficiently inhibited beta-catenin 
      protein levels, transcriptional activity, and proliferation of human renal 
      carcinoma cells with an activated beta-catenin pathway. Taken together, our results 
      provide novel molecular insights into the tumor suppressor activity of menin, 
      which is partly mediated by proteasomal degradation of beta-catenin and inhibition 
      of Wnt/beta-catenin signaling.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Kim, Byungho
AU  - Kim B
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea; C&C 
      Research Laboratories, Discovery Research Center, Sungkyunkwan University, Suwon 
      440-746, South Korea.
FAU - Song, Tae-Yang
AU  - Song TY
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
FAU - Jung, Kwan Young
AU  - Jung KY
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
FAU - Kim, Seul Gi
AU  - Kim SG
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
FAU - Cho, Eun-Jung
AU  - Cho EJ
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea. 
      Electronic address: echo@skku.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170804
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Ubiquitin)
RN  - 0 (beta Catenin)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Cells, Cultured
MH  - HEK293 Cells
MH  - Humans
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Binding
MH  - *Proteolysis
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Ubiquitin/*metabolism
MH  - beta Catenin/*metabolism
OTO - NOTNLM
OT  - Menin
OT  - Tumor suppressor
OT  - Ubiquitination
OT  - beta-catenin
EDAT- 2017/08/08 06:00
MHDA- 2017/09/26 06:00
CRDT- 2017/08/08 06:00
PHST- 2017/07/28 00:00 [received]
PHST- 2017/08/02 00:00 [accepted]
PHST- 2017/08/08 06:00 [pubmed]
PHST- 2017/09/26 06:00 [medline]
PHST- 2017/08/08 06:00 [entrez]
AID - S0006-291X(17)31547-4 [pii]
AID - 10.1016/j.bbrc.2017.08.011 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Oct 7;492(1):128-134. doi: 
      10.1016/j.bbrc.2017.08.011. Epub 2017 Aug 4.