Stimulation of hTAFII68 (NTD)‐mediated transactivation by v‐Src

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Abstract
The three genes hTAFII68, EWS, and TLS (called the TET family) encode related RNA binding proteins containing an RNA recognition motif and three glycine‐, arginine‐, and proline‐rich regions in the C‐terminus and a degenerated repeat containing the consensus sequence Ser‐Tyr‐Gly‐Gln‐Ser in the N‐terminus. In many human cancers, the N‐terminal portion of hTAFII68, EWS, or TLS is fused to the DNA binding domain of one of several transcription factors including Fli‐1, ERG, ETV1, E1AF, WT1, ATF‐1, CHOP, or TEC. We have recognized the presence of several potential tyrosine phosphorylation sites within the amino‐terminal domain of hTAFII68 and have investigated the potential effects of cytoplasmic signaling on hTAFII68 function. Herein, we find that hTAFII68 is phosphorylated on tyrosine residue(s) by ectopic expression of v‐Src protein tyrosine kinase in vitro and in vivo. The hTAFII68 protein can associated with the SH3 domains of several cell signaling proteins, including v‐Src protein tyrosine kinase. We also document that full‐length v‐Src can stimulate hTAFII68‐mediated transcriptional activation, whereas deletion mutants of v‐Src are unable to exert this effect. In addition, cellular Src activity appears important for hTAFII68 function since hTAFII68‐mediated transactivation is reduced in a dose‐dependent fashion by ectopic overexpression of a dominant‐negative mutant of Src. Taken together, our results suggest that the biological activities of hTAFII68 are linked to the cytoplasmic Src signal transduction pathway.