Skp2 promotes adipocyte differentiation via a p27{sup Kip1}-independent mechanism in primary mouse embryonic fibroblasts

Skp2, the substrate-binding subunit of an SCF ubiquitin ligase complex, is a key regulator of cell cycle progression that targets substrates for degradation by the 26S proteasome. We have now shown that ablation of Skp2 in primary mouse embryonic fibroblasts (MEFs) results both in impairment of adip...

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Published in:Biochemical and biophysical research communications 2009-02, Vol.379 (2)
Main Authors: Okada, Mitsuru, Sakai, Tamon, Nakamura, Takehiro, Tamamori-Adachi, Mimi, Kitajima, Shigetaka, Matsuki, Yasushi, Watanabe, Eijiro, Hiramatsu, Ryuji, Sakaue, Hiroshi, Department of Pharmacology, Kinki University School of Medicine, Osakasayama 589-8511, Kasuga, Masato, Research Institute, International Medical Center of Japan, Tokyo 162-8655
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ADENOVIRUS
BUILDUP
CELL CYCLE
FIBROBLASTS
GENE REGULATION
GENES
LIGASES
LIPIDS
MICE
RECEPTORS
RNA
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Summary:Skp2, the substrate-binding subunit of an SCF ubiquitin ligase complex, is a key regulator of cell cycle progression that targets substrates for degradation by the 26S proteasome. We have now shown that ablation of Skp2 in primary mouse embryonic fibroblasts (MEFs) results both in impairment of adipocyte differentiation and in the accumulation of the cyclin-dependent kinase inhibitor p27{sup Kip1}, a principal target of the SCF{sup Skp2} complex. Genetic ablation of p27{sup Kip1} in MEFs promoted both lipid accumulation and adipocyte-specific gene expression. However, depletion of p27{sup Kip1} by adenovirus-mediated RNA interference failed to correct the impairment of adipocyte differentiation in Skp2{sup -/-} MEFs. In contrast, troglitazone, a high-affinity ligand for peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), largely restored lipid accumulation and PPAR{gamma} gene expression in Skp2{sup -/-} MEFs. Our data suggest that Skp2 plays an essential role in adipogenesis in MEFs in a manner that is at least in part independent of regulation of p27{sup Kip1} expression.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.12.069