Physiological importance and identification of novel targets for the N-terminal acetyltransferase NatB
Physiological importance and identification of novel targets for the N-terminal acetyltransferase NatB
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DOI：
10.1128/ec.5.2.368-378.2006
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发表时间：
2006-02-01
期刊：
影响因子：
--
通讯作者：
Blomberg, A
中科院分区：
文献类型：
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作者：
Caesar, R;Warringer, J;Blomberg, A
酿酒酵母中的N-末端乙酰转移酶NatB由催化亚基Nat 3 p和相关亚基Mdm 20 p组成。在这里，我们扩展我们目前的知识NatB的生理作用相结合的蛋白质组学和表型组学的方法。我们发现，无论是NAT 3或MDM 20删除菌株在特定的应力条件下显示不同的生长速率和形态，表明这两个NatB亚基有部分单独的功能。早期报道的nat 3 Delta菌株的表型与肌动蛋白电缆的功能改变有关。然而，我们发现，点突变体的原肌球蛋白，抑制肌动蛋白电缆缺陷观察到的nat 3三角洲只有部分恢复野生型的生长和形态，表明存在功能重要的乙酰化无关的肌动蛋白电缆功能。预测的NatB底物在一组不同的生物过程中显著过度表达，主要与DNA加工和细胞周期进展有关。这些蛋白质中的三种，Cac 2 p，Pac 10 p和Swc 7 p，被鉴定为真正的NatB底物。为了确定N-末端乙酰化对蛋白质功能可能很重要，我们进行了大规模的比较表型分析，包括nat 3 Delta和缺失了参与细胞周期调控和DNA加工的假定NatB底物的菌株。通过这个程序，我们预测了31个蛋白质的N-末端乙酰化的功能重要性。
The N-terminal acetyltransferase NatB in Saccharomyces cerevisiae consists of the catalytic subunit Nat3p and the associated subunit Mdm20p. We here extend our present knowledge about the physiological role of NatB by a combined proteomics and phenomics approach. We found that strains deleted for either NAT3 or MDM20 displayed different growth rates and morphologies in specific stress conditions, demonstrating that the two NatB subunits have partly individual functions. Earlier reported phenotypes of the nat3 Delta strain have been associated with altered functionality of actin cables. However, we found that point mutants of tropomyosin that suppress the actin cable defect observed in nat3 Delta only partially restores wild-type growth and morphology, indicating the existence of functionally important acetylations unrelated to actin cable function. Predicted NatB substrates were dramatically overrepresented in a distinct set of biological processes, mainly related to DNA processing and cell cycle progression. Three of these proteins, Cac2p, Pac10p, and Swc7p, were identified as true NatB substrates. To identify N-terminal acetylations potentially important for protein function, we performed a large-scale comparative phenotypic analysis including nat3 Delta and strains deleted for the putative NatB substrates involved in cell cycle regulation and DNA processing. By this procedure we predicted functional importance of the N-terminal acetylation for 31 proteins.