Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis.
Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis.
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DOI：
10.1126/scisignal.2000526
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发表时间：
2010-01-12
影响因子：
7.3
通讯作者：
Hart GW
中科院分区：
文献类型：
--
作者：
Wang Z;Udeshi ND;Slawson C;Compton PD;Sakabe K;Cheung WD;Shabanowitz J;Hunt DF;Hart GW
与磷酸化一样，O-连接的β-N-乙酰氨基葡萄糖的加入(O-GlcN酰化)是一个普遍存在的可逆过程，它改变核蛋白和细胞质蛋白上的丝氨酸和苏氨酸残基。O-GlcNAc转移酶(O-GlcNAc Transfer ase，OGT)的过表达干扰了胞质分裂，促进了多倍体，但OGT对其细胞周期功能具有重要作用的分子靶点尚不清楚。在这里，我们确定了141个以前未知的蛋白质上的O-GlcNAc位点，它们在纺锤体组装和胞质分裂中发挥功能。许多这些O-GlcN酰化位点要么与已知的磷酸化位点相同，要么非常接近它们。此外，我们发现O-GlcN酰化改变了与有丝分裂纺锤体和中体相关的关键蛋白的磷酸化。OGT的强制过表达增加了细胞周期蛋白依赖性蛋白1(CDK1)的抑制磷酸化，并降低了CDK1靶蛋白的磷酸化。CDK1的磷酸化程度增加的原因是其上游激酶MYT1的激活增加，以及伴随而来的CDK1磷酸酶CDC25C转录的减少。OGT过表达还导致MYT1和CDC25C上游的Polo样激酶1的信使RNA表达和蛋白丰度降低。这些数据不仅说明了O-GlcN酰化和作为关键信号通路调节因子的蛋白质的磷酸化之间的串扰，而且还揭示了O-GlcN酰化在细胞分裂调控中的作用机制。
Like phosphorylation, the addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokinesis and promotes polyploidy, but the molecular targets of OGT that are important for its cell cycle functions are unknown. Here, we identify 141 previously unknown O-GlcNAc sites on proteins that function in spindle assembly and cytokinesis. Many of these O-GlcNAcylation sites are either identical to known phosphorylation sites or in close proximity to them. Furthermore, we found that O-GlcNAcylation altered the phosphorylation of key proteins associated with the mitotic spindle and midbody. Forced overexpression of OGT increased the inhibitory phosphorylation of cyclin-dependent kinase 1 (CDK1) and reduced the phosphorylation of CDK1 target proteins. The increased phosphorylation of CDK1 is explained by increased activation of its upstream kinase, MYT1, and by a concomitant reduction in the transcript for the CDK1 phosphatase, CDC25C. OGT overexpression also caused a reduction in both messenger RNA expression and protein abundance of Polo-like kinase 1, which is upstream of both MYT1 and CDC25C. The data not only illustrate the crosstalk between O-GlcNAcylation and phosphorylation of proteins that are regulators of crucial signaling pathways, but also uncover a mechanism for the role of O-GlcNAcylation in regulation of cell division.
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DOI：
10.1083/jcb.153.4.865
发表时间：
2001-05-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Adams RR;Maiato H;Earnshaw WC;Carmena M
通讯作者：
Carmena M
影响因子：
7.5
作者：
Carmena M;Ruchaud S;Earnshaw WC
通讯作者：
Earnshaw WC
影响因子：
64.8
作者：
Fuller, Brian G.;Lampson, Michael A.;Kapoor, Tarun M.
通讯作者：
Kapoor, Tarun M.
影响因子：
56.9
作者：
Daniels, MJ;Wang, YM;Venkitaraman, AR
通讯作者：
Venkitaraman, AR
影响因子：
56.9
作者：
MUELLER, PR;COLEMAN, TR;DUNPHY, WG
通讯作者：
DUNPHY, WG