Tumor suppressor stars in yeast G1/S transition
- PDF / 674,030 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 45 Downloads / 170 Views
MINI-REVIEW
Tumor suppressor stars in yeast G1/S transition Pan Li1 · Zhimin Hao1 · Fanli Zeng1 Received: 20 September 2020 / Revised: 22 October 2020 / Accepted: 28 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords G1/S transition · START · Tumor suppressor · Cip1 · p21 · Rb
Introduction Cell proliferation is a tightly regulated process where extracellular signals and intracellular checkpoints are integrated to control cell growth and division. When conditions for cell division are favorable, cells commit to enter the cell cycle during G1 phase at an irreversible transition termed START in yeast and the Restriction Point in mammalian cells (Pardee 1974), which is highly conserved in eukaryotes (Johnson and Skotheim 2013). Once the cell cycle G1/S transition is deregulated, cell proliferation will be uncontrolled, which is a hallmark of cancer (Gutschner and Diederichs 2012). In human cells, dysfunction of the G1/S checkpoint causes excessive cell division and promotes tumorigenesis (Massagué 2004). Many regulatory genes of the G1/S checkpoint are often detected with high-frequency mutations during the development of cancer. The earliest discovered Rb is considered to be the key regulatory gene of the G1/S transition, and
Communicated by M. Kupiec. * Fanli Zeng [email protected] 1
College of Life Sciences, Hebei Agricultural University, Baoding 071001, Hebei, China
Rb mutations have been found in in many types of cancer cells (Cooper 2006). Studies have shown that one of the most important mechanisms of tumor suppressor gene p53 and p21 mutations leading to cell carcinogenesis is the inactivation of G1/S transcriptional regulation (Barr et al. 2017; Engeland 2017). Therefore, studying tumor suppressor stars in G1/S checkpoint regulation mechanism will provide an important theoretical basis for clarifying how cancer cells continue to enter the proliferation cycle. Y
Data Loading...
