Abstract:
:Desmoplastic small round cell tumor (DSRCT) is a malignant human cancer that is associated with a specific t(11;22) chromosome translocation, where 265 amino acids from the EWS amino-terminus are fused to the DNA binding domain of the WT1 tumor suppressor gene. We have noticed the presence of several SH3 interacting domains within the amino-terminus of EWS and have assessed the potential of EWS/WT1 to interact with such motifs. We find that EWS/WT1 can associate with the SH3 domain of several proteins, including v-Src. Ectopic expression of v-Src phosphorylates EWS/WT1 in vivo, as well as enhances the transactivation ability of the EWS amino-terminal domain. Structural alteration of the v-Src SH2 or SH3 domains produced mutants that could not interact with EWS/WT1 nor augment the transcriptional properties of EWS. Taken together, our results suggest the possibility that some transcriptional properties of EWS/WT1 may be regulated by a cytoplasmic signaling pathway.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Kim J,Lee JM,Branton PE,Pelletier Jdoi
10.1016/s0014-5793(00)01590-8keywords:
subject
Has Abstractpub_date
2000-06-02 00:00:00pages
121-8issue
2-3eissn
0014-5793issn
1873-3468pii
S0014-5793(00)01590-8journal_volume
474pub_type
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