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J. Biol. Chem., Vol. 275, Issue 22, 16845-16850, June 2, 2000
From the Department of Nutritional Sciences, University of
California, Berkeley, California 94720
In an attempt to study molecules that play a
regulatory role early in adipocyte differentiation, we identified by
differential display ENC-1, a Drosophila kelch-related
protein. ENC-1 colocalizes with actin filaments. ENC-1 is expressed in
adipose tissue, specifically in the adipose-derived stroma-vascular
fraction. ENC-1 mRNA levels are transiently increased 8-12-fold
early in in vitro adipocyte differentiation of primary
cells of the adipose-derived stroma-vascular fraction and of 3T3-L1
cells. Treatment with the adipogenic inducers dexamethasone and
methylisobutylxanthine causes an increase in ENC-1 mRNA levels
specifically in preadipocytes, and methylisobutylxanthine is the main
effector of ENC-1 expression. The induction of ENC-1 precedes
expression of the transcription factors, peroxisome
proliferator-activated receptor (PPAR
Transient Induction of ENC-1, a Kelch-related Actin-binding
Protein, Is Required for Adipocyte Differentiation*
, and
) and
CCAAT/enhancer-binding protein (C/EBP
), and other adipocyte markers
including adipocyte fatty acid-binding protein. The ENC-1 induction
correlates with the subsequent differentiation of primary
stroma-vascular cells into adipocytes. Furthermore, decreasing the
endogenous ENC-1 levels by stable antisense transfection, thereby
preventing the transient induction, effectively inhibits 3T3-L1
adipocyte differentiation. Overall, these studies indicate that ENC-1,
an actin-binding protein, plays a regulatory role early in adipocyte
differentiation when cytoskeletal reorganization and cell shape change
from fibroblastic preadipocytes to spherical adipocytes occur.
*
This work was supported by National Institutes of Health
Grant RO1 DK 50828 (to H. S. S.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Parke-Davis Laboratory for Molecular Genetics,
1501 Harbor Bay Parkway, Alameda, CA 94502.
§
To whom correspondence should be addressed. Tel.: 510-642-3978;
Fax: 510-642-0535; E-mail: hsul@nature.berkeley.edu.
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