细胞大小严重缺陷是癌细胞几乎普遍存在的特征，然而其潜在原因尚不清楚。之前的研究指出，酵母Ras的超活化突变体（ras2G19V）与人类Ras癌基因类似，可能导致细胞大小缺陷，从而有助于解析癌基因如何影响细胞大小。然而，ras2G19V如何影响细胞大小的机制尚不明确。本研究发现，ras2G19V抑制细胞周期进入的关键步骤，早期G1期细胞周期素诱导晚期G1期细胞周期素的转录。因此，ras2G19V促使早期G1期细胞周期素Cln3的过度表达，但Cln3未能诱导正常的晚期G1期细胞周期素转录，导致细胞周期进入延迟和细胞大小增加。ras2G19V通过一个尚不明确的步骤影响晚期G1期细胞周期素的转录，此步骤中Cln3使Whi5转录抑制因子失活。之前的研究发现，酵母Ras通过蛋白激酶A（PKA）传递信号；然而，ras2G19V似乎通过新的PKA非依赖信号机制影响晚期G1期细胞周期素的表达。综上所述，这些数据揭示了超活化Ras如何影响酵母细胞周期进入和细胞大小的新机制。超活化Ras也会影响哺乳动物细胞G1期细胞周期素的表达，但机制尚不清楚。进一步分析酵母中的Ras信号传导可能有助于发现Ras家族成员控制G1期细胞周期素表达的新机制。© 2023作者。由牛津大学出版社代表The Genetics Society of America发表。版权所有。如需获取授权，请发送电子邮件至：journals.permissions@oup.com。

Severe defects in cell size are a nearly universal feature of cancer cells. However, the underlying causes are unknown. A previous study suggested that a hyperactive mutant of yeast Ras (ras2G19V) that is analogous to the human Ras oncogene causes cell size defects, which could provide clues to how oncogenes influence cell size. However, the mechanisms by which ras2G19V influences cell size are unknown. Here, we found that ras2G19V inhibits a critical step in cell cycle entry, in which an early G1 phase cyclin induces transcription of late G1 phase cyclins. Thus, ras2G19V drives overexpression of the early G1 phase cyclin Cln3, yet Cln3 fails to induce normal transcription of late G1 phase cyclins, leading to delayed cell cycle entry and increased cell size. ras2G19V influences transcription of late G1 phase cyclins via a poorly understood step in which Cln3 inactivates the Whi5 transcriptional repressor. Previous studies found that yeast Ras relays signals via protein kinase A (PKA); however, ras2G19V appears to influence late G1 phase cyclin expression via novel PKA-independent signaling mechanisms. Together, the data define new mechanisms by which hyperactive Ras influences cell cycle entry and cell size in yeast. Hyperactive Ras also influences expression of G1 phase cyclins in mammalian cells, but the mechanisms remain unclear. Further analysis of Ras signaling in yeast could lead to discovery of new mechanisms by which Ras family members control expression of G1 phase cyclins.© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.