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PMID:10937998

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Citation

Ross, SE, Hemati, N, Longo, KA, Bennett, CN, Lucas, PC, Erickson, RL and MacDougald, OA (2000) Inhibition of adipogenesis by Wnt signaling. Science 289:950-3

Abstract

Wnts are secreted signaling proteins that regulate developmental processes. Here we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch that governs adipogenesis. Wnt signaling maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator- activated receptor gamma (PPARgamma). When Wnt signaling in preadipocytes is prevented by overexpression of Axin or dominant-negative TCF4, these cells differentiate into adipocytes. Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination.

Links

PubMed

Keywords

3T3 Cells; Adipocytes/cytology; Adipocytes/metabolism; Animals; Axin Protein; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Lineage; Cytoskeletal Proteins/metabolism; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Gene Transfer Techniques; Genetic Vectors; Mesoderm/cytology; Mice; Mice, Nude; Muscles/cytology; Muscles/metabolism; Nuclear Proteins/antagonists & inhibitors; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Proteins/genetics; Proteins/metabolism; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Repressor Proteins; Retroviridae/genetics; Retroviridae/physiology; Signal Transduction; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors/antagonists & inhibitors; Transcription Factors/genetics; Transcription Factors/metabolism; Wnt Proteins; Zebrafish Proteins; beta Catenin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:WN10B

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WN10B

acts_upstream_of_or_within

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0048625: myoblast fate commitment

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TF7L2

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TF7L2

acts_upstream_of_or_within

GO:0045599: negative regulation of fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TF7L2

involved_in

GO:0048625: myoblast fate commitment

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TF7L2

involved_in

GO:0045444: fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WN10B

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WN10B

involved_in

GO:0050821: protein stabilization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AXIN1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AXIN1

acts_upstream_of_or_within

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT1

acts_upstream_of_or_within

GO:0045599: negative regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT1

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PPARG

acts_upstream_of_or_within

GO:0045444: fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CEBPA

acts_upstream_of_or_within

GO:0045600: positive regulation of fat cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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