PMID- 26403202
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20240405
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 128
IP  - 21
DP  - 2015 Nov 1
TI  - Rac1 augments Wnt signaling by stimulating beta-catenin-lymphoid enhancer factor-1 
      complex assembly independent of beta-catenin nuclear import.
PG  - 3933-46
LID - 10.1242/jcs.167742 [doi]
AB  - beta-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads 
      to gene transactivation and cancer. Rac1 GTPase is known to stimulate 
      beta-catenin-dependent transcription of Wnt target genes and we confirmed this 
      activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling 
      by enhancing beta-catenin nuclear import; however, we found that 
      silencing/inhibition or up-regulation of Rac1 had no influence on nuclear 
      accumulation of beta-catenin. To better define the role of Rac1, we employed 
      proximity ligation assays (PLA) and discovered that a significant pool of 
      Rac1-beta-catenin protein complexes redistribute from the plasma membrane to the 
      nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to 
      stimulate the formation of nuclear beta-catenin-lymphoid enhancer factor 1 (LEF-1) 
      complexes. This regulation required Rac1-dependent phosphorylation of beta-catenin 
      at specific serines, which when mutated (S191A and S605A) reduced beta-catenin 
      binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation 
      experiments. We propose that Rac1-mediated phosphorylation of beta-catenin 
      stimulates Wnt-dependent gene transactivation by enhancing beta-catenin-LEF-1 
      complex assembly, providing new insight into the mechanism of cross-talk between 
      Rac1 and canonical Wnt/beta-catenin signaling.
CI  - (c) 2015. Published by The Company of Biologists Ltd.
FAU - Jamieson, Cara
AU  - Jamieson C
AD  - Center for Cancer Research, The Westmead Millennium Institute for Medical 
      Research, The University of Sydney, Westmead, New South Wales 2145, Australia.
FAU - Lui, Christina
AU  - Lui C
AD  - Center for Cancer Research, The Westmead Millennium Institute for Medical 
      Research, The University of Sydney, Westmead, New South Wales 2145, Australia.
FAU - Brocardo, Mariana G
AU  - Brocardo MG
AD  - Center for Cancer Research, The Westmead Millennium Institute for Medical 
      Research, The University of Sydney, Westmead, New South Wales 2145, Australia.
FAU - Martino-Echarri, Estefania
AU  - Martino-Echarri E
AD  - Center for Cancer Research, The Westmead Millennium Institute for Medical 
      Research, The University of Sydney, Westmead, New South Wales 2145, Australia.
FAU - Henderson, Beric R
AU  - Henderson BR
AD  - Center for Cancer Research, The Westmead Millennium Institute for Medical 
      Research, The University of Sydney, Westmead, New South Wales 2145, Australia 
      beric.henderson@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150924
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (beta Catenin)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Active Transport, Cell Nucleus/genetics/physiology
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - HCT116 Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Lymphoid Enhancer-Binding Factor 1/genetics/*metabolism
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Real-Time Polymerase Chain Reaction
MH  - Wnt Signaling Pathway/genetics/physiology
MH  - beta Catenin/genetics/*metabolism
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
PMC - PMC4657330
OTO - NOTNLM
OT  - Proximity ligation assay
OT  - Rac1
OT  - Wnt signaling
OT  - beta-Catenin
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2015/09/26 06:00
MHDA- 2016/09/23 06:00
PMCR- 2015/11/01
CRDT- 2015/09/26 06:00
PHST- 2014/12/17 00:00 [received]
PHST- 2015/09/17 00:00 [accepted]
PHST- 2015/09/26 06:00 [entrez]
PHST- 2015/09/26 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - jcs.167742 [pii]
AID - JCS167742 [pii]
AID - 10.1242/jcs.167742 [doi]
PST - ppublish
SO  - J Cell Sci. 2015 Nov 1;128(21):3933-46. doi: 10.1242/jcs.167742. Epub 2015 Sep 
      24.