PMID- 19883644
OWN - NLM
STAT- MEDLINE
DCOM- 20100121
LR  - 20211203
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 584
IP  - 1
DP  - 2010 Jan 4
TI  - Depletion of mammalian target of rapamycin (mTOR) via siRNA mediated knockdown 
      leads to stabilization of beta-catenin and elicits distinct features of 
      cardiomyocyte hypertrophy.
PG  - 74-80
LID - 10.1016/j.febslet.2009.10.080 [doi]
AB  - Cardiac myocyte growth is under differential control of mammalian target of 
      rapamycin (mTOR) and glycogen-synthase-kinase-3beta (GSK3beta). Whereas active 
      GSK3beta negatively regulates growth and down-regulates cellular protein 
      synthesis, activation of the mTOR pathway promotes protein expression and cell 
      growth. Here we report that depletion of mTOR via siRNA mediated knockdown causes 
      marked down-regulation of GSK3beta protein in cardiac myocytes. As a result, 
      GSK3beta target protein beta-catenin becomes stabilized and translocates into the 
      nucleus. Moreover, mTOR knockdown leads to increase in cardiac myocyte surface 
      area and produces an up-regulation of the fetal gene program. Our findings 
      suggest a new type of convergence of mTOR and GSK3beta activities, indicating 
      that GSK3beta-dependent stabilization of beta-catenin in cardiac myocytes is 
      influenced by mTOR.
FAU - Hagenmueller, Marco
AU  - Hagenmueller M
AD  - Department of Cardiology, University of Heidelberg, Heidelberg, Germany. 
      marco.hagenmueller@med.uni-heidelberg.de
FAU - Malekar, Pratima
AU  - Malekar P
FAU - Fieger, Christiane
AU  - Fieger C
FAU - Weiss, Celine S
AU  - Weiss CS
FAU - Buss, Sebastian J
AU  - Buss SJ
FAU - Wolf, David
AU  - Wolf D
FAU - Katus, Hugo A
AU  - Katus HA
FAU - Hardt, Stefan E
AU  - Hardt SE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (RNA, Small Interfering)
RN  - 0 (beta Catenin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/genetics/*metabolism/pathology
MH  - Cells, Cultured
MH  - Gene Knockdown Techniques
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Myocytes, Cardiac/*metabolism/pathology
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein Stability
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - beta Catenin/*metabolism
EDAT- 2009/11/04 06:00
MHDA- 2010/01/22 06:00
CRDT- 2009/11/04 06:00
PHST- 2009/08/13 00:00 [received]
PHST- 2009/10/20 00:00 [revised]
PHST- 2009/10/27 00:00 [accepted]
PHST- 2009/11/04 06:00 [entrez]
PHST- 2009/11/04 06:00 [pubmed]
PHST- 2010/01/22 06:00 [medline]
AID - S0014-5793(09)00872-2 [pii]
AID - 10.1016/j.febslet.2009.10.080 [doi]
PST - ppublish
SO  - FEBS Lett. 2010 Jan 4;584(1):74-80. doi: 10.1016/j.febslet.2009.10.080.