Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Biosci Biotechnol Biochem. 2021 May 25;85(6):1452-1459. doi: 10.1093/bbb/zbab056.
eIF4E-binding proteins (4E-BPs) are translational repressors that compete with eIF4G for binding to eIF4E. Here we investigated the roles of yeast 4E-BPs, Eap1, and Caf20 in cell wall integrity pathway and gene expression. We found that eap1∆ mutation, but not caf20∆ mutation, showed synthetic growth defect with mutation in ROM2 gene encoding Rho1 GEF. The eap1∆ mutation also showed synthetic lethality with mutation in CCR4 gene encoding cytoplasmic deadenylase. Ccr4 functions in the degradation of LRG1 mRNA encoding Rho1 GAP. Eap1-Y109A L114A, which could not bind to eIF4E, did not suppress the synthetic lethality of eap1∆ ccr4∆ mutant, suggesting that 4E-binding of Eap1 is important for its function. We also found that eap1∆ mutant showed the derepression of stress response gene HSP12. 4E-binding of Eap1 was also required for the repression of HSP12 expression. Our results indicate that Eap1 has similar but independent roles in cell growth and gene expression with Ccr4.
真核起始因子 4E 结合蛋白（eIF4E-binding proteins，4E-BPs）是翻译抑制剂，可与 eIF4G 竞争与 eIF4E 结合。在这里，我们研究了酵母 4E-BP 蛋白 Eap1 和 Caf20 在细胞壁完整性途径和基因表达中的作用。我们发现，eap1Δ 突变体与编码 Rho1 GEF 的 ROM2 基因突变体表现出合成生长缺陷，但 caf20Δ 突变体没有。eap1Δ 突变体也与编码细胞质脱腺苷酶的 CCR4 基因突变体表现出合成致死性。Ccr4 参与编码 Rho1 GAP 的 LRG1 mRNA 的降解。不能与 eIF4E 结合的 Eap1-Y109A L114A 突变体不能抑制 eap1Δ ccr4Δ 突变体的合成致死性，表明 Eap1 与 4E 的结合对于其功能很重要。我们还发现 eap1Δ 突变体表现出应激反应基因 HSP12 的去抑制。Eap1 与 4E 的结合对于 HSP12 表达的抑制也是必需的。我们的结果表明，Eap1 在细胞生长和基因表达中具有与 Ccr4 相似但独立的作用。
