Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.
Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.
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DOI：
10.1074/jbc.m310240200
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发表时间：
2004-03-19
期刊：
影响因子：
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通讯作者：
O'Rahilly S
中科院分区：
文献类型：
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作者：
Laudes M;Christodoulides C;Sewter C;Rochford JJ;Considine RV;Sethi JK;Vidal-Puig A;O'Rahilly S
痘病毒锌指（POZ）锌指结构域转录因子已被证明在几种类型的间充质细胞的生长停滞和分化的控制中发挥作用，但还没有，脂肪细胞。我们发现，POZ结构域蛋白，因子结合到短转录本-1（FBI-1）的诱导剂，诱导在小鼠和人类前脂肪细胞分化与最大表达水平在第2-4天。FBI-1 mRNA在人类脂肪组织中表达，在病态肥胖受试者的样本中表达水平最高。组成型表达FBI-1的小鼠细胞系显示出加速脂肪形成的证据，早期诱导分化标志物和增强脂质积累，表明FBI-1可能是分化过程中的积极参与者。与其他细胞系统中该蛋白质家族的性质一致，稳定过表达FBI-1的3 T3 L1细胞显示DNA合成减少和细胞周期蛋白A、细胞周期蛋白依赖性激酶2和p107的表达减少，这些蛋白质已知参与有丝分裂克隆扩增的调节。此外，FBI-1降低了细胞周期蛋白A启动子的转录活性。因此，FBI-1，POZ锌指转录因子，诱导在人类和小鼠前脂肪细胞分化的早期阶段，它可能有助于脂肪形成，通过影响从细胞增殖到终末分化的开关。
Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2–4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation.