期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 3, 页码 850-855出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0337434100
关键词
3T3-L1 preadipocyte; mouse embryo fibroblasts; C/EBP alpha; PPAR gamma; cell cycle
资金
- NIDDK NIH HHS [DK38418, DK61840, K01 DK61355, R01 DK038418, K01 DK061355, F32 DK061840] Funding Source: Medline
Hormonal induction of growth-arrested 3T3-L1 preadipocytes triggers a signaling cascade that culminates in adipogenesis. CCAAT/enhancer-binding protein (C/EBP)beta is expressed immediately but gains DNA-binding activity only after a long lag as the cells synchronously begin mitotic clonal expansion (MCE). After MCE, a process required for adipogenesis, C/EBPbeta activates expression of C/EBPalpha and peroxisome proliferator-activated receptor gamma, which then transcriptionally activate genes that produce the adipocyte phenotype. When mouse embryo fibroblasts (MEFs) are subjected to the same differentiation protocol, a subset of the MEFs undergoes a similar program of events. Similar to 3T3-L1 preadipocytes, the MEFs reenter the cell cycle (as indicated by the synchronous expression of cyclin A) and undergo MCE as evidenced by the incorporation of BrdUrd into DNA and the formation of mitotic foci of cells that undergo adipogenesis. C/EBPbeta is expressed immediately after induction but exhibits delayed acquisition of DNA-binding activity followed by expression of adipocyte markers and the accumulation of cytoplasmic triglyceride. MEFs from C/EBPbeta(-/-) mice, however, neither undergo MCE nor differentiate into adipocytes. Forced expression of C/EBPbeta (LAP) but not dominant-negative C/EBPbeta (LIP) in C/EBPbeta(-/-) MEFs restores MCE, expression of adipocyte markers, and the capacity to form mitotic foci of cells that undergo adipogenesis. These findings demonstrate that expression of C/EBPbeta is a prerequisite for MCE in the adipocyte-differentiation program.
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