Baroni M D, Monti P, Alberghina L
Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, Italy.
Nature. 1994 Sep 22;371(6495):339-42. doi: 10.1038/371339a0.
A yeast cell becomes committed to the cell division cycle only if it grows to a critical size and reaches a critical rate of protein synthesis. The coordination between growth and division takes place at a control step during the G1 phase of the cell cycle called Start. It relies on the G1-specific cyclins encoded by CLN1, 2 and 3, which trigger Start through the activation of the Cdc28 protein kinase. In fact, the Cln cyclins are rate-limiting for Start execution and depend on growth. Here we report that the cyclic AMP signal pathway modulates the dependency of Cln cyclins on growth. In particular, more growth is required to trigger Start because CLN1 and CLN2 are repressed by the cAMP signal, thus explaining the previously observed cAMP-dependent increase of the critical size and critical rate of protein synthesis. Cln3 is not inhibited by the cAMP pathway and counteracts this mechanism by partially mediating the growth-dependent expression of other G1 cyclins.
酵母细胞只有在生长到临界大小并达到临界蛋白质合成速率时,才会进入细胞分裂周期。生长与分裂之间的协调发生在细胞周期G1期的一个称为“起始点”(Start)的控制步骤中。它依赖于由CLN1、2和3编码的G1期特异性细胞周期蛋白,这些蛋白通过激活Cdc28蛋白激酶来触发起始点。实际上,Cln细胞周期蛋白是起始点执行的限速因素,并且依赖于生长。我们在此报告,环磷酸腺苷(cAMP)信号通路调节Cln细胞周期蛋白对生长的依赖性。特别是,由于CLN1和CLN2受到cAMP信号的抑制,因此需要更多的生长才能触发起始点,这就解释了先前观察到的cAMP依赖性的临界大小增加和蛋白质合成临界速率增加的现象。Cln3不受cAMP信号通路的抑制,并通过部分介导其他G1期细胞周期蛋白的生长依赖性表达来抵消这一机制。