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Science 17 April 1992:
Vol. 256. no. 5055, pp. 379 - 382
DOI: 10.1126/science.256.5055.379

Articles

Reciprocal Regulation of Adipogenesis by Myc and C/EBPagr

Svend O. Freytag 1 and Tim J. Geddes 2

1 Molecular Biology Research Program, Henry Ford Hospital, Detroit, Ml 48202, and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Ml 48109
2 Molecular Biology Research Program, Henry Ford Hospital, Detroit, Ml 48202

3T3-L1 adipoblasts that express large amounts of c-Myc cannot terminally differentiate, raising the possibility that Myc inhibits the expression of genes that promote adipogenesis. The CCAAT/enhancer binding protein (C/EBPagr) is induced during 3T3-L1 adipogenesis when cells commit to the differentiation pathway. Transfection of 3T3-L1 adipoblasts with the gene that encodes C/EBPagr caused overt expression of the adipocyte morphology. Expression of Myc prohibited the normal induction of C/EBPagr and prevented adipogenesis. Enforced expression of C/EBPagr overcame the Myc-induced block to differentiation. These results provide a molecular basis for the regulation of adipogenesis and implicate Myc and C/EBPagr as pivotal controlling elements.


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   Abstract »    PDF »
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A. M. Diehl, D. C. Johns, S. Yang, H. Lin, M. Yin, L. A. Matelis, and J. H. Lawrence (1996)
J. Biol. Chem. 271, 7343-7350
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1..
A J Wagner, J M Kokontis, and N Hay (1994)
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   Abstract »    PDF »
Novel mechanism of C/EBP beta (NF-M) transcriptional control: activation through derepression..
E Kowenz-Leutz, G Twamley, S Ansieau, and A Leutz (1994)
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   Abstract »    PDF »
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H Zinszner, R Albalat, and D Ron (1994)
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   Abstract »    PDF »
The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site..
S R Hann, M Dixit, R C Sears, and L Sealy (1994)
Genes & Dev. 8, 2441-2452
   Abstract »    PDF »
Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells..
S O Freytag, D L Paielli, and J D Gilbert (1994)
Genes & Dev. 8, 1654-1663
   Abstract »    PDF »
mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer..
P Tontonoz, E Hu, R A Graves, A I Budavari, and B M Spiegelman (1994)
Genes & Dev. 8, 1224-1234
   Abstract »    PDF »
CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest..
M V Barone, A Crozat, A Tabaee, L Philipson, and D Ron (1994)
Genes & Dev. 8, 453-464
   Abstract »    PDF »
Proadipocyte cell lines: models of cellular proliferation and differentiation.
M. Smyth, R. Sparks, and W Wharton (1993)
J. Cell Sci. 106, 1-9
   PDF »
Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development..
P Rorth and D J Montell (1992)
Genes & Dev. 6, 2299-2311
   Abstract »    PDF »
Functional Antagonism between Msx2 and CCAAT/Enhancer-binding Protein alpha in Regulating the Mouse Amelogenin Gene Expression Is Mediated by Protein-Protein Interaction.
Y. L. Zhou, Y. Lei, and M. L. Snead (2000)
J. Biol. Chem. 275, 29066-29075
   Abstract »    Full Text »    PDF »
Generation of Truncated C/EBPbeta Isoforms by in Vitro Proteolysis.
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J. Biol. Chem. 275, 26582-26590
   Abstract »    Full Text »    PDF »
Mitotic Clonal Expansion during Preadipocyte Differentiation: Calpain-mediated Turnover of p27.
Y. M. Patel and M. D. Lane (2000)
J. Biol. Chem. 275, 17653-17660
   Abstract »    Full Text »    PDF »
Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking.
M. Fukuda, J. E. Moreira, V. Liu, M. Sugimori, K. Mikoshiba, and R. R. Llinas (2000)
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   Abstract »    Full Text »    PDF »



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