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 adipogenisis and identify new targets for the modulation of adipogenesis.
Highlights
The current epidemic of obesity and diabetes has stimulated research to improve the understanding of these diseases and to identify and characterize new genes involved in their pathogenesis [1,2,3,4,5]
We identified 13 potential interacting partners for ANKRD26 by yeast two-hybrid screening, and validated as novel ANKRD26 interacting proteins triple functional domain protein (TRIO), G protein pathway suppressor 2 (GPS2), delta-interacting protein A (DIPA), and hyaluronan-mediated motility receptor (HMMR) by co-immunoprecipitation assays in mammalian cells
Our analysis of adipogenesis showed that the selective down-regulation of Ankyrin repeat domain 26 (Ankrd26), triple functional domain protein (Trio), G-protein pathway suppressor 2 (Gps2), Hmmr and Dipa, increased adipocyte differentiation upon induction in 3T3-L1 cells
Summary
The current epidemic of obesity and diabetes has stimulated research to improve the understanding of these diseases and to identify and characterize new genes involved in their pathogenesis [1,2,3,4,5]. Mice with partial inactivation of the Ankrd gene develop marked hyperphagia, severe obesity and an unusual form of diabetes in which white adipose tissue preserves its sensitivity to insulin [6,7]. The protein is located in the cytosol close to the inner aspect of the cell membrane in HeLa and 293T cells expressing ANKRD26-EGFP, and it contains both ankyrin repeats and spectrin helices, through which it is potentially able to interact with other proteins [6]. It is not yet known what these proteins are and how the Ankrd protein carries out its biological functions
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