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对Elm1激酶活性的特异性抑制揭示了G1早期事件所需的功能。

Specific inhibition of Elm1 kinase activity reveals functions required for early G1 events.

作者信息

Sreenivasan Aparna, Bishop Anthony C, Shokat Kevan M, Kellogg Douglas R

机构信息

Sinsheimer Laboratories, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, California 95064, USA.

出版信息

Mol Cell Biol. 2003 Sep;23(17):6327-37. doi: 10.1128/MCB.23.17.6327-6337.2003.

Abstract

In budding yeast, the Elm1 kinase is required for coordination of cell growth and cell division at G(2)/M. Elm1 is also required for efficient cytokinesis and for regulation of Swe1, the budding yeast homolog of the Wee1 kinase. To further characterize Elm1 function, we engineered an ELM1 allele that can be rapidly and selectively inhibited in vivo. We found that inhibition of Elm1 kinase activity during G(2) results in a phenotype similar to the phenotype caused by deletion of the ELM1 gene, as expected. However, inhibition of Elm1 kinase activity earlier in the cell cycle results in a prolonged G(1) delay. The G(1) requirement for Elm1 kinase activity occurs before bud emergence, polarization of the septins, and synthesis of G(1) cyclins. Inhibition of Elm1 kinase activity during early G(1) also causes defects in the organization of septins, and inhibition of Elm1 kinase activity in a strain lacking the redundant G(1) cyclins CLN1 and CLN2 is lethal. These results demonstrate that the Elm1 kinase plays an important role in G(1) events required for bud emergence and septin organization.

摘要

在出芽酵母中,Elm1激酶是细胞在G(2)/M期协调细胞生长和细胞分裂所必需的。Elm1对于有效的胞质分裂以及对Wee1激酶的出芽酵母同源物Swe1的调控也是必需的。为了进一步表征Elm1的功能,我们构建了一个ELM1等位基因,其在体内能够被快速且选择性地抑制。正如预期的那样,我们发现G(2)期Elm1激酶活性的抑制导致的表型与ELM1基因缺失所导致的表型相似。然而,在细胞周期早期抑制Elm1激酶活性会导致G(1)期延长。对Elm1激酶活性在G(1)期的需求发生在芽出现、隔膜蛋白极化以及G(1)期细胞周期蛋白合成之前。在G(1)早期抑制Elm1激酶活性也会导致隔膜蛋白组织出现缺陷,并且在缺乏冗余G(1)期细胞周期蛋白CLN1和CLN2的菌株中抑制Elm1激酶活性是致死的。这些结果表明,Elm1激酶在芽出现和隔膜蛋白组织所需的G(1)期事件中起重要作用。

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