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首页> 外文期刊>Molecular and Cellular Biology >The p21-Activated Protein Kinase Inhibitor Skb15 and Its Budding Yeast Homologue Are 60S Ribosome Assembly Factors
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The p21-Activated Protein Kinase Inhibitor Skb15 and Its Budding Yeast Homologue Are 60S Ribosome Assembly Factors

机译：p21激活的蛋白激酶抑制剂Skb15及其芽酵母同源物是60S核糖体装配的因素。

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Ribosome biogenesis is driven by a large number of preribosomal factors that associate with and dissociate from the preribosomal particles along the maturation pathway. We have previously shown that budding yeast Mak11, whose homologues in other eukaryotes were described as modulating a p21-activated protein kinase function, accumulates in Rlp24-associated pre-60S complexes when their maturation is impeded in Saccharomyces cerevisiae. The functional inactivation of WD40 repeat protein Mak11 interfered with the 60S rRNA maturation, led to a cell cycle delay in G1, and blocked green fluorescent protein-tagged Rpl25 in the nucleoli of yeast cells, indicating an early role of Mak11 in ribosome assembly. Surprisingly, Mak11 inactivation also led to a dramatic destabilization of Rlp24. The suppression of the thermosensitive phenotype of a mak11 mutant by RLP24 overexpression and a direct in vitro interaction between Rlp24 and Mak11 suggest that Mak11 acts as an Rlp24 cofactor during early steps of 60S ribosomal subunit assembly. Moreover, we found that Skb15, the Mak11 homologue in Schizosaccharomyces pombe, also associated with preribosomes and affected 60S biogenesis in fission yeast. It is thus likely that the previously observed phenotypes for MAK11 homologues in other eukaryotes are secondary to the main function of these proteins in ribosome formation.
机译：核糖体的生物发生是由大量的核糖体前因子驱动的，这些因子沿着成熟途径与核糖体前颗粒相关或分离。我们以前已经证明，发芽酵母Mak11（在其他真核生物中的同源物被描述为调节p21激活的蛋白激酶功能）会在酿酒酵母中阻止其成熟时，在Rlp24相关的60S前复合物中积累。 。 WD40重复蛋白Mak11的功能失活会干扰60S rRNA的成熟，导致G 1 的细胞周期延迟，并阻止酵母细胞核中带有绿色荧光蛋白标签的Rpl25，这表明早期Mak11在核糖体装配中的作用。令人惊讶的是，Mak11的失活也导致Rlp24的急剧失稳。 RLP24 过表达抑制 mak11 突变体的热敏表型以及Rlp24和Mak11之间的直接体外相互作用表明，Mak11在60S的早期过程中充当Rlp24辅助因子核糖体亚基组装。此外，我们发现Skb15，即粟酒裂殖酵母中的Mak11同源物，也与核糖体有关，并影响了裂变酵母中的60S生物发生。因此，以前在其他真核生物中观察到的 MAK11 同源物表型可能是继这些蛋白在核糖体形成过程中起主要作用的第二位。

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