Yeast is one of the best-understood biological systems for genetic research. Over the last 40 years, geneticists have striven to search for homologues of tumor suppressors in yeast to simplify cancer research. The star tumor suppressor p21, downstream target of p53, is one of the primary factors on the START point through negatively regulating CycD/E-CDK, the yeast counterpart Cln3-Cdk1. Not like yeast Whi5 that was identified as the analog of the retinoblastoma tumor suppressor protein (Rb) and hence promoted to uncover the mechanism of its cancer suppression, homologue of p21 had not been found in yeast. Our lab identified Cip1 in budding yeast as a novel negative regulator of G1-Cdk1 and proposed that Cip1 is an analog of human p21. Recently, we demonstrated a dual repressive function of Cip1 on START timing via the redundant Cln3 and Ccr4 pathways. This work in yeast may help clarify the complex regulation in human p53-p21 signaling cascade. In this review, we will discuss the yeast paralogs of star tumor suppressors in the control of G1/S transition and present the new findings in this field.

酵母是基因研究中最容易理解的生物系统之一。在过去的 40 年里，遗传学家一直在努力寻找酵母中肿瘤抑制基因的同源物，以简化癌症研究。星形肿瘤抑制因子 p21 是 p53 的下游靶标，通过负调节 CycD/E-CDK（酵母对应物 Cln3-Cdk1）是 START 点的主要因素之一。不像酵母 Whi5 被鉴定为视网膜母细胞瘤肿瘤抑制蛋白 (Rb) 的类似物并因此促进揭示其癌症抑制机制，在酵母中尚未发现 p21 的同源物。我们的实验室将出芽酵母中的 Cip1 鉴定为 G1-Cdk1 的新型负调节因子，并提出 Cip1 是人类 p21 的类似物。最近，我们通过冗余的 Cln3 和 Ccr4 通路证明了 Cip1 在 START 时间上的双重抑制功能。酵母中的这项工作可能有助于阐明人类 p53-p21 信号级联反应中的复杂调控。在这篇综述中，我们将讨论控制 G1/S 过渡的星形肿瘤抑制基因的酵母旁系同源物，并介绍该领域的新发现。