PMID- 23512667
OWN - NLM
STAT- MEDLINE
DCOM- 20141023
LR  - 20211021
IS  - 1099-0844 (Electronic)
IS  - 0263-6484 (Print)
IS  - 0263-6484 (Linking)
VI  - 32
IP  - 1
DP  - 2014 Jan
TI  - Muscle ring finger 1 and muscle ring finger 2 are necessary but functionally 
      redundant during developmental cardiac growth and regulate E2F1-mediated gene 
      expression in vivo.
PG  - 39-50
LID - 10.1002/cbf.2969 [doi]
AB  - AIMS: Muscle ring finger (MuRF) proteins have been implicated in the transmission 
      of mechanical forces to nuclear cell signaling pathways through their association 
      with the sarcomere. We recently reported that MuRF1, but not MuRF2, regulates 
      pathologic cardiac hypertrophy in vivo. This was surprising given that MuRF1 and 
      MuRF2 interact with each other and many of the same sarcomeric proteins 
      experimentally. METHODS AND RESULTS: Mice missing all four MuRF1 and MuRF2 
      alleles [MuRF1/MuRF2 double null (DN)] were born with a massive spontaneous 
      hypertrophic cardiomyopathy and heart failure; mice that were null for one of the 
      genes but heterozygous for the other (i.e. MuRF1(-/-) //MuRF2(+/-) or MuRF1(+/-) 
      //MuRF2(-/-) ) were phenotypically identical to wild-type mice. Microarray 
      analysis of genes differentially-expressed between MuRF1/MuRF2 DN, mice missing 
      three of the four alleles and wild-type mice revealed a significant enrichment of 
      genes regulated by the E2F transcription factor family. More than 85% of the 
      differentially-expressed genes had E2F promoter regions (E2f:DP; P<0.001). 
      Western analysis of E2F revealed no differences between MuRF1/MuRF2 DN hearts and 
      wild-type hearts; however, chromatin immunoprecipitation studies revealed that 
      MuRF1/MuRF2 DN hearts had significantly less binding of E2F1 in the promoter 
      regions of genes previously defined to be regulated by E2F1 (p21, Brip1 and PDK4, 
      P<0.01). CONCLUSIONS: These studies suggest that MuRF1 and MuRF2 play a redundant 
      role in regulating developmental physiologic hypertrophy, by regulating E2F 
      transcription factors essential for normal cardiac development by supporting E2F 
      localization to the nucleus, but not through a process that degrades the 
      transcription factor.
CI  - Copyright (c) 2013 John Wiley & Sons, Ltd.
FAU - Willis, Monte S
AU  - Willis MS
AD  - McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA; 
      Department of Pathology and Laboratory Medicine, University of North Carolina, 
      Chapel Hill, NC, USA.
FAU - Wadosky, Kristine M
AU  - Wadosky KM
FAU - Rodriguez, Jessica E
AU  - Rodriguez JE
FAU - Schisler, Jonathan C
AU  - Schisler JC
FAU - Lockyer, Pamela
AU  - Lockyer P
FAU - Hilliard, Eleanor G
AU  - Hilliard EG
FAU - Glass, David J
AU  - Glass DJ
FAU - Patterson, Cam
AU  - Patterson C
LA  - eng
GR  - R37HL065619/HL/NHLBI NIH HHS/United States
GR  - T32 HL069768/HL/NHLBI NIH HHS/United States
GR  - T32 HL083828/HL/NHLBI NIH HHS/United States
GR  - R01 HL065619/HL/NHLBI NIH HHS/United States
GR  - R01 HL104129/HL/NHLBI NIH HHS/United States
GR  - R37 HL065619/HL/NHLBI NIH HHS/United States
GR  - R01HL104129/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130320
PL  - England
TA  - Cell Biochem Funct
JT  - Cell biochemistry and function
JID - 8305874
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (E2f1 protein, mouse)
RN  - 0 (Muscle Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - 0 (muscle RING finger 2 protein, mouse)
RN  - EC 2.3.2.27 (Trim63 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cardiomegaly/genetics/*metabolism
MH  - E2F1 Transcription Factor/genetics/metabolism
MH  - Gene Expression
MH  - Heart/growth & development/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle Proteins/genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Sarcomeres/metabolism
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
PMC - PMC3728166
MID - NIHMS460310
OTO - NOTNLM
OT  - E2F
OT  - MuRF1
OT  - MuRF2
OT  - cardiac hypertrophy
OT  - ubiquitin ligase
COIS- Conflict of Interest The authors have declared that no conflict of interest 
      exists (M.W., J.R., K.W., J.S.,P.L., E.H., D.G., C.P.).
EDAT- 2013/03/21 06:00
MHDA- 2014/10/24 06:00
PMCR- 2015/01/01
CRDT- 2013/03/21 06:00
PHST- 2012/10/02 00:00 [received]
PHST- 2013/02/03 00:00 [revised]
PHST- 2013/02/14 00:00 [accepted]
PHST- 2013/03/21 06:00 [entrez]
PHST- 2013/03/21 06:00 [pubmed]
PHST- 2014/10/24 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - 10.1002/cbf.2969 [doi]
PST - ppublish
SO  - Cell Biochem Funct. 2014 Jan;32(1):39-50. doi: 10.1002/cbf.2969. Epub 2013 Mar 
      20.