Journal of Biochemistry Advance Access published online on December 13, 2006
Journal of Biochemistry, doi:10.1093/jb/mvm018
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© 2006 The Japanese Biochemical Society
Orphan nuclear receptor Nur77 accelerates the initial phase of adipocyte differentiation in 3T3-L1 cells by promoting mitotic clonal expansion
Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, Kamigori, Hyogo 678-1297
*To whom correspondence should be addressed. 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan. TEL: +81-791-58-0192, FAX: +81-791-58-0193, E-mail: osumi{at}sci.u-hyogo.ac.jp
Received November 21, 2006; Accepted November 27, 2006
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Abstract |
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Nur77 is an orphan member of the nuclear receptor superfamily that is expressed in various types of cells and mediates diverse biological processes. Although Nur77 mRNA is induced in the early stage of adipogenesis of 3T3-L1 cells, its roles are not known. To address this issue, we closely inspected the expression of Nur77 mRNA and protein during differentiation of 3T3-L1 cells. Nur77 was induced rapidly and transiently at both mRNA and protein levels only in the initial phase of differentiation induction, and localized almost exclusively in the nuclei. Isobutylmethylxanthine was essential for the induction of Nur77 protein, acting by at least in part protecting the protein from rapid degradation by proteasome. Nur77 siRNA resulted in delayed adipogenesis in 3T3-L1, accompanied by retarded mitotic clonal expansion. These effects were mediated at least partly by decreased expression of cyclins D and E. Constitutive expression of Nur77 inhibited adipogenesis of 3T3-L1, accompanied by enhanced expression of cyclin D1 and prolonged mitotic clonal expansion. Moreover, constitutive expression of Nur77 inhibited, but transient induction of Nur77 promoted, adipogenesis in NIH-3T3 cells. These results suggest that Nur77 accelerates adipocyte differentiation by regulating cell cycle progression and the rapid and transient induction is crucial for its action.
Key Words: adipocyte differentiation, cyclin, clonal expansion, NIH-3T3, Nur77, 3T3-L1
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