PMID- 17962384
OWN - NLM
STAT- MEDLINE
DCOM- 20080709
LR  - 20211020
IS  - 0888-8809 (Print)
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Linking)
VI  - 22
IP  - 2
DP  - 2008 Feb
TI  - Modulator recognition factor-2 is required for adipogenesis in mouse embryo 
      fibroblasts and 3T3-L1 cells.
PG  - 441-53
AB  - Previous study showed that mice lacking modulator recognition factor-2 (Mrf-2) 
      were lean, with significant decreases in white adipose tissue. One postulated 
      mechanism for the lean phenotype in Mrf-2 knockout mice is a defect in 
      adipogenesis. In order to investigate this further, we examined the effects of 
      Mrf-2 deficiency on adipogenesis in vitro. In mouse fibroblasts (MEFs) derived 
      from Mrf-2(-/-) embryos, and in 3T3-L1 cells after knockdown of Mrf-2 by small 
      interference RNA (siRNA) there was a potent inhibition of hormone-induced lipid 
      accumulation, and significant decreases in the expression of the adipogenic 
      transcription factors CCAAT/enhancer-binding protein (C/EBP) alpha and peroxisome 
      proliferator-activated receptor-gamma and the mature adipocyte genes they 
      control. Transduction of Mrf-2(-/-) MEFs with a retroviral vector expressing the 
      longer Mrf-2 splice variant (Mrf-2B) stimulated both gene expression and lipid 
      accumulation. Because 3T3-L1 cells are committed to the adipocyte lineage, we 
      used this simpler model system to examine the effects of Mrf-2 deficiency on 
      adipocyte maturation. Analyses of both mRNA and protein revealed that knockdown 
      of Mrf-2 in 3T3-L1 cells prolonged the expression of C/EBP homologous protein-10, 
      a dominant-negative form of C/EBP. Consistent with these findings, suppression of 
      Mrf-2 also inhibited the DNA-binding activity of C/EBPbeta. These data suggest 
      that Mrf-2 facilitates the induction of the two key adipogenic transcription 
      factors C/EBPalpha and peroxisome proliferator-activated receptor-gamma 
      indirectly by permitting hormone-mediated repression of the adipogenic repressor 
      C/EBP homologous protein-10.
FAU - Yamakawa, Takahiro
AU  - Yamakawa T
AD  - Department of Molecular Biology, City of Hope Beckman Research Institute, 1500 
      East Duarte Road, Duarte, CA 91010, USA.
FAU - Whitson, Robert H
AU  - Whitson RH
FAU - Li, Shu-Lian
AU  - Li SL
FAU - Itakura, Keiichi
AU  - Itakura K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071025
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Arid5b protein, mouse)
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipogenesis/*genetics
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-alpha/genetics/metabolism
MH  - Cell Differentiation/genetics
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Embryonic Stem Cells/cytology/metabolism
MH  - Fibroblasts/cytology/*metabolism
MH  - Gene Deletion
MH  - Gene Expression Regulation, Developmental
MH  - Immunoblotting
MH  - Mice
MH  - Models, Genetic
MH  - Mutation
MH  - PPAR gamma/genetics/metabolism
MH  - Protein Binding
MH  - RNA, Small Interfering/genetics
MH  - Transcription Factors/*genetics/metabolism
PMC - PMC5419636
EDAT- 2007/10/27 09:00
MHDA- 2008/07/10 09:00
PMCR- 2009/02/01
CRDT- 2007/10/27 09:00
PHST- 2007/10/27 09:00 [pubmed]
PHST- 2008/07/10 09:00 [medline]
PHST- 2007/10/27 09:00 [entrez]
PHST- 2009/02/01 00:00 [pmc-release]
AID - me.2007-0271 [pii]
AID - 10.1210/me.2007-0271 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2008 Feb;22(2):441-53. doi: 10.1210/me.2007-0271. Epub 2007 Oct 
      25.