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PMID:17576771

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Citation

Naiki, T, Saijou, E, Miyaoka, Y, Sekine, K and Miyajima, A (2007) TRB2, a mouse Tribbles ortholog, suppresses adipocyte differentiation by inhibiting AKT and C/EBPbeta. J. Biol. Chem. 282:24075-82

Abstract

Adipocyte differentiation is regulated by a complex array of extracellular signals, intracellular mediators and transcription factors. Here we describe suppression of adipocyte differentiation by TRBs, mammalian orthologs of Drosophila Tribbles. Whereas all the three TRBs were expressed in 3T3-L1 preadipocytes, TRB2 and TRB3, but not TRB1, were immediately down-regulated by differentiation stimuli. Forced expression of TRB2 and TRB3 inhibited adipocyte differentiation at an early stage. Akt activation is a key event in adipogenesis and was severely inhibited by TRB3 in 3T3-L1 cells. However, the inhibition by TRB2 was mild compared with severe inhibition by TRB3, though TRB2 suppressed adipogenesis as strongly as TRB3. Interestingly, TRB2 but not TRB3 reduced the level of C/EBPbeta, a transcription factor required for an early stage of adipogenesis, through a proteasome-dependent mechanism. Furthermore, knockdown of endogenous TRB2 by siRNA allowed 3T3-L1 cells to differentiate without full differentiation stimuli. These results suggest that inhibition of Akt activation in combination with degradation of C/EBPbeta is the basis for the strong inhibitory effect of TRB2 on adipogenesis.

Links

PubMed Online version:10.1074/jbc.M701409200

Keywords

3T3-L1 Cells; Adipocytes/cytology; Adipogenesis; Animals; CCAAT-Enhancer-Binding Protein-beta/antagonists & inhibitors; Cell Cycle Proteins/physiology; Cell Differentiation; Intracellular Signaling Peptides and Proteins/physiology; Mice; Protein-Serine-Threonine Kinases/physiology; Proto-Oncogene Proteins c-akt/antagonists & inhibitors; RNA, Small Interfering/pharmacology

Significance

Annotations

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

MOUSE:TRIB3

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:TRIB2

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TRIB2

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRIB2

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8K4K3

P

Seeded From UniProt

complete

HUMAN:TRIB2

enables

GO:0061629: RNA polymerase II-specific DNA-binding transcription factor binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8K4K3

F

Seeded From UniProt

complete

HUMAN:TRIB3

involved_in

GO:0045599: negative regulation of fat cell differentiation

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8K4K2

P

Seeded From UniProt

complete


See also

References

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