Tumor suppressor stars in yeast G1/S transition.

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.