Abstract
Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C-terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenesis and identify new targets for the modulation of adipogenesis.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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3T3-L1 Cells
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Adipogenesis*
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Animals
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Carrier Proteins / metabolism*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Extracellular Matrix Proteins / deficiency
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Extracellular Matrix Proteins / genetics
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Extracellular Matrix Proteins / metabolism*
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Gene Expression Regulation
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Gene Knockdown Techniques
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Guanine Nucleotide Exchange Factors / deficiency
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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HEK293 Cells
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Humans
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Hyaluronan Receptors / genetics
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Hyaluronan Receptors / metabolism*
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Immunoprecipitation
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins / deficiency
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Binding
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein Transport
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Reproducibility of Results
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Two-Hybrid System Techniques
Substances
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Ankrd26 protein, mouse
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Carrier Proteins
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DIPA protein, mouse
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DNA-Binding Proteins
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Extracellular Matrix Proteins
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GPS2 protein, mouse
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Guanine Nucleotide Exchange Factors
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Hyaluronan Receptors
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Transcription Factors
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Trio protein, mouse
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hyaluronan-mediated motility receptor
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Protein Serine-Threonine Kinases