Phosphorylation of Ewing's sarcoma protein (EWS) and EWS-Fli1 in response to DNA damage.
Phosphorylation of Ewing's sarcoma protein (EWS) and EWS-Fli1 in response to DNA damage.
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DOI：
10.1042/bj20082097
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
Iva Klevernic;Simon Morton;R. Davis;P. Cohen
中科院分区：
文献类型：
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作者：
Iva Klevernic;Simon Morton;R. Davis;P. Cohen
在尤文氏肉瘤中，染色体易位导致EWS（尤文氏肉瘤蛋白）的N-末端结构域与Ets（E26转化特异性）转录因子家族的DNA结合结构域融合。在这里，我们表明，EWS和EWS-Fli 1（朋友白血病病毒整合1），融合最常见的尤因肉瘤，成为磷酸化的Thr（79）在有丝分裂原或DNA损伤剂。促分裂原诱导的EWS磷酸化作用较弱，由MAPK（促分裂原活化蛋白激酶）、ERK 1（细胞外信号调节激酶1）和ERK 2催化，而由DNA烷化剂MMS（甲磺酸甲酯）诱导的EWS磷酸化作用较强，可由JNK（c-Jun N-末端激酶）和至少一种不同于ERK 1/ERK 2的其他蛋白激酶催化。与此相反，MMS诱导的EWS-Fli 1磷酸化主要由p38 α/p38 β MAPK介导。MMS诱导的EWS-Fli 1的磷酸化比EWS在异源二聚体，包括这两种蛋白质。
In Ewing's sarcomas, chromosomal translocations cause the N-terminal domain of the EWS (Ewing's sarcoma protein) to fuse with the DNA-binding domains of the Ets (E26 transformation-specific) family of transcription factors. Here we show that EWS and EWS-Fli1 (Friend leukaemia virus integration 1), the fusion most frequently found in Ewing's sarcomas, become phosphorylated at Thr(79) in response to either mitogens or DNA-damaging agents. The much weaker mitogen-induced phosphorylation of EWS is catalysed by the MAPKs (mitogen-activated protein kinases) ERK1 (extracellular signal-regulated kinase 1) and ERK2, whereas the much stronger phosphorylation of EWS induced by the DNA alkylating agent MMS (methyl methanesulphonate) can be catalysed by JNK (c-Jun N-terminal kinase) and at least one other protein kinase distinct from ERK1/ERK2. In contrast, the phosphorylation of EWS-Fli1 induced by MMS was largely mediated by p38alpha/p38beta MAPKs. MMS induced a much stronger phosphorylation of EWS-Fli1 than EWS in heterodimers comprising both proteins.