Nature of the critical labile event that controls RB phosphorylation in the cyclic AMP-dependent cell cycle of thyrocytes in primary culture.
Nature of the critical labile event that controls RB phosphorylation in the cyclic AMP-dependent cell cycle of thyrocytes in primary culture.
复制标题
原代培养中甲状腺细胞环 AMP 依赖性细胞周期中控制 RB 磷酸化的关键不稳定事件的性质。
作者：
P. Roger;S. Demartin;J. Dumont
这项研究解决了关键不稳定事件的本质，该事件在限制点有丝分裂级联与细胞周期的自主部分耦合。在狗甲状腺上皮细胞的原代培养物中，动力学实验表明不稳定的 cAMP 依赖性事件正控制 G1 晚期对 DNA 复制和 RB 磷酸化的承诺。如该系统之前所示，cAMP 依赖性有丝分裂途径与最普遍设想的生长因子级联不同，因为它刺激 p27(kip1) 的积累，但不刺激细胞周期蛋白 D 的积累。然而，细胞周期蛋白 D3 和 CDK4 活性在 cAMP 依赖性有丝分裂发生中至关重要，并且 cAMP 揭示细胞周期蛋白 D3 的 DCS-22 表位并诱导细胞周期蛋白 D3 和 CDK4 的核易位和组装在还包含 p27(kip1) 的复合物中。出乎意料的是，毛喉素的清洗迅速阻止了S期进入和过度磷酸化RB的积累，但没有逆转与细胞周期蛋白D3-CDK4激活相关的任何上述事件。这意味着，即使在诱导稳定的细胞周期蛋白 D3-CDK4 复合物后，狗甲状腺细胞仍然依赖于 cAMP 进行 RB 磷酸化和 DNA 合成，这表明在狗甲状腺细胞和可能的其他系统的 cAMP 依赖性细胞周期中，负责限制点通道最后控制的关键不稳定事件仍有待发现。
This study addresses the nature of the critical labile event that couples at restriction point mitogenic cascades with the autonomous part of the cell cycle. In primary cultures of dog thyroid epithelial cells, kinetic experiments indicate that a labile cAMP-dependent event positively controls a late G1 commitment to DNA replication and RB phosphorylation. As previously shown in this system, the cAMP-dependent mitogenic pathway differs from the most generally envisaged growth factor cascades as it stimulates the accumulation of p27(kip1) but not of cyclins D. Nevertheless, cyclin D3 and CDK4 activity are essential in the cAMP-dependent mitogenesis, and cAMP unmasks the DCS-22 epitope of cyclin D3 and induces the nuclear translocations and assembly of cyclin D3 and CDK4 in a complex that also contains p27(kip1). Unexpectedly, the washing out of forskolin rapidly arrested S phase entry and the accumulation of hyperphosphorylated RB, but did not reverse any of the above events associated with cyclin D3-CDK4 activation. This implies that even after induction of stable nuclear cyclin D3-CDK4 complexes, dog thyrocytes still depend on cAMP for RB phosphorylation and commitment to DNA synthesis, which suggests that a key labile event responsible for a last control of restriction point passage remains to be uncovered, in the cAMP-dependent cell cycle of dog thyrocytes and possibly other systems.
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