近日，来自美国斯坦福大学的研究人员在著名国际学术期刊nature上发表了一项最新研究进展，他们在出芽酵母中发现在细胞分裂之前，周期蛋白Cln3的合成速率随细胞尺寸变化，而转录抑制因子Whi5的浓度会随细胞生长而得到稀释，通过这种机制实现了细胞尺寸对增殖的调控。
细胞的大小是影响细胞内所有生物合成过程的基础，它决定了细胞器的尺寸还影响着细胞的物质运输。虽然大量研究已经发现了许多影响细胞大小的基因，但细胞尺寸调控之下隐藏的分子机制仍然没有得到完全揭示。
对于出芽酵母Saccharomyces cerevisiae来说，细胞尺寸调控在进入细胞分裂起始点之前就已经出现于细胞周期的G1期，之前一直认为G1 期周期蛋白 Cln3的活性会随着细胞尺寸增加，并通过抑制转录抑制因子Whi5触发细胞分裂起始点。
在这项研究中，研究人员发现Cln3的浓度会调节细胞通过分裂起始点的速度，而它的合成会随着细胞尺寸的变大而逐渐增加，因此在细胞分裂之前的G1期，Cln3的总浓度仍然会接近恒定。相比于Cln3的活性增加，研究人员还发现Whi5的活性发生下降，主要是因为细胞生长导致Whi5的浓度得到稀释，细胞通过这种分子机制实现了利用细胞尺寸调节细胞增殖的目的。
研究人员发现Whi5的合成主要发生于细胞周期的S/G2/M期，并以细胞尺寸非依赖性方式进行合成。这导致更小的子代细胞一形成就含有更高浓度的Whi5，并一直持续到分裂前的G1期。因此，出芽酵母的尺寸调控是Cln3和Whi5的合成速率随细胞尺寸变化的结果。
总的来说，这项工作表明蛋白质合成存在不同的尺寸依赖性，这一发现为进一步研究细胞功能与生长的协调性机制提供了重要信息。
Dilution of the cell cycle inhibitor Whi5 controls budding-yeast cell size
Kurt M. Schmoller,J. J. Turner,M. K?ivom?gi & Jan M. Skotheim
Cell size fundamentally affects all biosynthetic processes by determining the scale of organelles and influencing surface transport1, 2. Although extensive studies have identified many mutations affecting cell size, the molecular mechanisms underlying size control have remained elusive3. In the budding yeast Saccharomyces cerevisiae, size control occurs in G1 phase before Start, the point of irreversible commitment to cell division4, 5. It was previously thought that activity of the G1 cyclin Cln3 increased with cell size to trigger Start by initiating the inhibition of the transcriptional inhibitor Whi5 (refs 6, 7, 8). Here we show that although Cln3 concentration does modulate the rate at which cells pass Start, its synthesis increases in proportion to cell size so that its total concentration is nearly constant during pre-Start G1. Rather than increasing Cln3 activity, we identify decreasing Whi5 activity-due to the dilution of Whi5 by cell growth-as a molecular mechanism through which cell size controls proliferation. Whi5 is synthesized in S/G2/M phases of the cell cycle in a largely size-independent manner. This results in smaller daughter cells being born with higher Whi5 concentrations that extend their pre-Start G1 phase. Thus, at its most fundamental level, size control in budding yeast results from the differential scaling of Cln3 and Whi5 synthesis rates with cell size. More generally, our work shows that differential size-dependency of protein synthesis can provide an elegant mechanism to coordinate cellular functions with growth.