Aurora B opposes PP1 function in mitosis by phosphorylating the conserved PP1-binding RVxF motif in PP1 regulatory proteins.
Aurora B opposes PP1 function in mitosis by phosphorylating the conserved PP1-binding RVxF motif in PP1 regulatory proteins.
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DOI：
10.1126/scisignal.aai8669
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发表时间：
2018-05-15
影响因子：
7.3
通讯作者：
Moorhead GB
中科院分区：
文献类型：
--
作者：
Nasa I;Rusin SF;Kettenbach AN;Moorhead GB
蛋白磷酸酶1(PP1)是一种高度保守的蛋白磷酸酶，执行真核生物中大部分的丝氨酸和苏氨酸(Ser-Thr)去磷酸化反应，并对抗一系列不同的Ser-Thr蛋白激酶的作用。PP1通过与控制PP1定位、活性和与底物相互作用的大量调节蛋白(>；200)结合来获得底物特异性。PP1识别许多这些调节蛋白中存在的特征良好的RVxF结合基序，从而产生大量不同的PP1全酶。在这里，我们证明了RVxF结合基序的子集，其中x是一个可磷酸化的氨基酸(RV[S/T]F)，在有丝分裂过程中被特异性地磷酸化，这种磷酸化事件取消了PP1与调节蛋白的相互作用。我们确定这种磷酸化主要由有丝分裂蛋白激酶Aurora B控制，这些位点的高磷酸化位点化学计量比通过破坏PP1全酶的组装维持了有丝分裂期间PP1底物的磷酸化。我们产生了一种抗体，可以识别RV[S/T]F基序(RVP[S/T]F)的磷酸化形式，并用它来识别已知的PP1调节蛋白(KNL1、CDCA2和Rif1)以及受这一机制控制的多种可能作为PP1结合伙伴的蛋白(UBR5、ASPM、SEH1和Elys)。综上所述，本文提出了一种通用的调控机制，通过该机制，Aurora B和PP1的协调活动控制有丝分裂的进展。
Protein phosphatase 1 (PP1) is a highly conserved protein phosphatase that performs the majority of serine and threonine (Ser-Thr) dephosphorylation reactions in eukaryotes and opposes the actions of a diverse set of Ser-Thr protein kinases. PP1 gains substrate specificity through binding to a large number (> 200) of regulatory proteins that control PP1 localization, activity, and interactions with substrates. PP1 recognizes the well-characterized RVxF binding motif that is present in many of these regulatory proteins, thus generating a multitude of distinct PP1 holoenzymes. Here we show that a subset of the RVxF binding motifs, in which x is a phosphorylatable amino acid (RV[S/T]F), were phosphorylated specifically during mitosis and that this phosphorylation event abrogated the interaction of PP1 with the regulatory protein. We determined that this phosphorylation was primarily governed by the mitotic protein kinase Aurora B and that high phosphorylation site stoichiometry of these sites maintained phosphorylation of PP1 substrates during mitosis by disrupting the assembly of PP1 holoenzymes. We generated an antibody that recognizes the phosphorylated form of the RV[S/T]F motif (RVp[S/T]F) and used it to identify known PP1 regulatory proteins (KNL1, CDCA2, and RIF1) as well as multiple proteins that could potentially act as PP1 binding partners (UBR5, ASPM, SEH1, and ELYS) governed by this mechanism. Taken together, the work presented here suggests a general regulatory mechanism by which the coordinated activities of Aurora B and PP1 control mitotic progression.
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影响因子：
7.3
作者：
Kettenbach AN;Schweppe DK;Faherty BK;Pechenick D;Pletnev AA;Gerber SA
通讯作者：
Gerber SA
影响因子：
4.8
作者：
Hurley, Thomas D.;Yang, Jie;DePaoli-Roach, Anna A.
通讯作者：
DePaoli-Roach, Anna A.
影响因子：
3.4
作者：
Eng, Jimmy K.;Jahan, Tahmina A.;Hoopmann, Michael R.
通讯作者：
Hoopmann, Michael R.
影响因子：
13.8
作者：
Bollen, Mathieu;Peti, Wolfgang;Ragusa, Michael J.;Beullens, Monique
通讯作者：
Beullens, Monique
DOI：
10.1083/jcb.200710019
发表时间：
2008-04-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Emanuele MJ;Lan W;Jwa M;Miller SA;Chan CS;Stukenberg PT
通讯作者：
Stukenberg PT