Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.
Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.
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DOI：
10.1242/bio.20122956
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发表时间：
2013-01-15
期刊：
影响因子：
2.4
通讯作者：
Srayko M
中科院分区：
文献类型：
--
作者：
Lange KI;Heinrichs J;Cheung K;Srayko M
蛋白质磷酸化和去磷酸化是许多基本发育过程的时空调控的关键机制，在有丝分裂期间尤为突出。多亚基蛋白磷酸酶2A（PP 2A）酶在有丝分裂过程中蛋白质的去磷酸化中起着重要的作用，但其特征尚不清楚。PP 2A是包含催化、结构和调节亚基的异源三聚体复合物。调节亚基是相互排斥的，并决定亚细胞定位和底物特异性的PP 2A。至少存在3种不同类型的调节亚基（称为B、B′、B″），但这些类型之间的一级序列没有明显的相似性。因此，目前尚不清楚这些不同的调节亚基如何与相同的全酶相互作用，以促进特定的PP 2A在体内的功能。调节亚基的B“家族是最不了解的，因为这些蛋白质缺乏保守的结构域。RSA-1（regulator of spindle assembly）是秀丽隐杆线虫纺锤体组装所必需的一个调控B″亚基。为了解决B“亚基如何与PP 2A核心酶相互作用，我们将重点放在条件等位基因rsa-1（或598 ts）上，并确定该突变特异性地破坏RSA-1和PP 2A结构亚基PAA-1之间的蛋白质相互作用。通过遗传学筛选，我们确定了PAA-1结构亚基上与RSA-1/B“的确定区域相互作用的假定界面。在先前发表的结果的背景下，这些数据提出了一种机制，不同的PP 2A B-调节亚基家族如何以相互排斥的方式结合相同的全酶，在体内执行特定的任务。
Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.
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影响因子：
3.7
作者：
O'Toole E;Greenan G;Lange KI;Srayko M;Müller-Reichert T
通讯作者：
Müller-Reichert T
DOI：
10.1083/jcb.200202047
发表时间：
2002-05-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hannak E;Oegema K;Kirkham M;Gönczy P;Habermann B;Hyman AA
通讯作者：
Hyman AA
影响因子：
64.5
作者：
Griffin EE;Odde DJ;Seydoux G
通讯作者：
Seydoux G
DOI：
10.1016/j.bbrc.2009.06.096
发表时间：
2009-09-04
影响因子：
3.1
作者：
Janssens, Veerle;Derua, Rita;Goris, Jozef
通讯作者：
Goris, Jozef
影响因子：
3.7
作者：
O'Rourke, Sean M.;Carter, Clayton;Bowerman, Bruce
通讯作者：
Bowerman, Bruce