Hodge A, Mendenhall M
L.P. Markey Cancer Center, University of Kentucky, Lexington 40536-0096, USA.
Mol Gen Genet. 1999 Aug;262(1):55-64. doi: 10.1007/s004380051059.
By inhibiting the activity of Cdc28/Clb cyclin-dependent protein kinase (CDK) complexes, Sic1 prevents the premature initiation of S phase in the yeast Saccharomyces cerevisiae. By testing a series of Sic1 truncation mutants, we have mapped the minimal domain necessary for Cdc28/Clb inhibition in vivo to the C-terminal 70 amino acids of Sic1. Site-directed mutagenesis was used to show that a sequence that matches the zRxL motif found in mammalian CDK inhibitors is essential for Sicl function. This motif is not found in the Schizosaccharomyces CDK inhibitor p25rum1, which appears to be a structural and functional homolog of Sicl. Based on the mutational data and sequence comparisons, we argue that Sic1 and p25rum1 are structurally distinct from the known mammalian CDK inhibitors, but may bind CDK complexes in a manner more closely resembling CDK substrates like the retinoblastoma and E2F proteins.
通过抑制Cdc28/Clb细胞周期蛋白依赖性蛋白激酶（CDK）复合物的活性，Sic1可防止酿酒酵母中S期的过早起始。通过测试一系列Sic1截短突变体，我们已将体内抑制Cdc28/Clb所需的最小结构域定位到Sic1的C末端70个氨基酸。定点诱变用于表明与哺乳动物CDK抑制剂中发现的zRxL基序匹配的序列对Sicl功能至关重要。在粟酒裂殖酵母CDK抑制剂p25rum1中未发现该基序，p25rum1似乎是Sicl的结构和功能同源物。基于突变数据和序列比较，我们认为Sic1和p25rum1在结构上与已知的哺乳动物CDK抑制剂不同，但可能以更类似于视网膜母细胞瘤和E2F蛋白等CDK底物的方式结合CDK复合物。
