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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitotic clonal expansion: A synchronous process required for adipogenesis
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Mitotic clonal expansion: A synchronous process required for adipogenesis

机译：有丝分裂克隆扩增：成脂所需的同步过程

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When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The preadipocytes traverse the G(1)/S checkpoint synchronously as evidenced by the expression/activation of cdk2-cyclin-E/A, turnover of p27/kip1, hyperphosphorylation of Rb, translocation of cyclin D-1 from nuclei to cytoplasm and GSK-3beta from cytoplasm to nuclei, and incorporation of [H-3]thymidine into DNA. As the cells cross the G(1)/S checkpoint, C/EBPbeta acquires DNA-binding activity, initiating a cascade of transcriptional activation that culminates in the expression of adipocyte proteins. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059 delays, but does not block, MCE and differentiation, the extent of the delay causing a comparable delay in the expression of cell-cycle markers, MCE, and adipogenesis. The more potent and specific MEK inhibitor UO126 and the cyclin-dependent kinase inhibitor roscovitine, which inhibit the cell cycle at different points, block MICE, expression of cell cycle and adipocyte markers, as well as adipogenesis. These results show that MCE is a prerequisite for differentiation of 3T3-L1 preadipocytes into adipocytes. [References: 38]
机译：当被诱导分化时，生长停滞的3T3-L1前脂肪细胞会同时重新进入细胞周期并经历有丝分裂克隆扩增（MCE），然后表达产生脂肪细胞表型的基因。前脂肪细胞通过cdk2-cyclin-E / A的表达/激活，p27 / kip1的更新，Rb的过度磷酸化，细胞周期蛋白D-1从细胞核到细胞质和GSK的转运而同步穿过G（1）/ S检查点。 -3beta从细胞质到细胞核，并将[H-3]胸苷掺入DNA。当细胞穿过G（1）/ S检查点时，C / EBPbeta获得DNA结合活性，从而引发一系列转录激活，最终达到脂肪细胞蛋白的表达。有丝分裂原激活的蛋白激酶/细胞外信号调节激酶激酶（MEK）抑制剂PD98059延迟但不阻断MCE和分化，这种延迟的程度在细胞周期标志物，MCE和脂肪形成。更有效和特异的MEK抑制剂UO126和细胞周期蛋白依赖性激酶抑制剂roscovitine，它们在不同点抑制细胞周期，阻断MICE，细胞周期和脂肪细胞标志物的表达以及脂肪形成。这些结果表明，MCE是将3T3-L1前脂肪细胞分化为脂肪细胞的先决条件。 [参考：38]

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