Phosphorylation of Ewing's sarcoma protein (EWS) and EWS-Fli1 in response to DNA damage
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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.
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Citation: Biochem J. 2009 Mar 15;418(3):625-34. doi: 10.1042/BJ20082097. Link to article on publisher's site
Klevernic, Iva V.; Morton, Simon; Davis, Roger J.; and Cohen, Philip, "Phosphorylation of Ewing's sarcoma protein (EWS) and EWS-Fli1 in response to DNA damage" (2009). Davis Lab. 74.