Gallego C, Garí E, Colomina N, Herrero E, Aldea M
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Rovira Roure 44, 25198 Lleida, Catalunya, Spain.
EMBO J. 1997 Dec 1;16(23):7196-206. doi: 10.1093/emboj/16.23.7196.
Nutrients are among the most important trophic factors in all organisms. When deprived of essential nutrients, yeast cells use accumulated reserves to complete the current cycle and arrest in the following G1 phase. We show here that the Cln3 cyclin, which has a key role in the timely activation of SBF (Swi4-Swi6)- and MBF (Mbp1-Swi6)-dependent promoters in late G1, is down-regulated rapidly at a post-transcriptional level in cells deprived of the nitrogen source. In addition to the fact that Cln3 is degraded faster by ubiquitin-dependent mechanisms, we have found that translation of the CLN3 mRNA is repressed approximately 8-fold under nitrogen deprivation conditions. As a consequence, both SBF- and MBF-dependent expression is strongly down-regulated. Mainly because of their transcriptional dependence on SBF, and perhaps with the contribution of similar post-transcriptional mechanisms to those found for Cln3, the G1 cyclins Cln1 and 2 become undetectable in starved cells. The complete loss of Cln cyclins and the sustained presence of the Clb-cyclin kinase inhibitor Sic1 in starved cells may provide the molecular basis for the G1 arrest caused by nitrogen deprivation.
营养物质是所有生物体中最重要的营养因子之一。当缺乏必需营养物质时,酵母细胞会利用积累的储备来完成当前周期,并在随后的G1期停滞。我们在此表明,Cln3细胞周期蛋白在G1晚期对SBF(Swi4-Swi6)和MBF(Mbp1-Swi6)依赖性启动子的及时激活中起关键作用,在缺乏氮源的细胞中,它在转录后水平迅速下调。除了Cln3通过泛素依赖性机制降解更快这一事实外,我们还发现,在氮剥夺条件下,CLN3 mRNA的翻译被抑制了约8倍。因此,SBF和MBF依赖性表达均被强烈下调。主要由于它们对SBF的转录依赖性,也许还有与Cln3类似的转录后机制的作用,G1细胞周期蛋白Cln1和Cln2在饥饿细胞中变得无法检测到。饥饿细胞中Cln细胞周期蛋白的完全丧失以及Clb细胞周期蛋白激酶抑制剂Sic1的持续存在可能为氮剥夺导致的G1停滞提供分子基础。