Modulation of EWS/WT1 activity by the v-Src protein tyrosine kinase.

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 Lett

journal_title

FEBS letters

authors

Kim J,Lee JM,Branton PE,Pelletier J

doi

10.1016/s0014-5793(00)01590-8

keywords:

subject

Has Abstract

pub_date

2000-06-02 00:00:00

pages

121-8

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)01590-8

journal_volume

474

pub_type

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