Stimulation of hTAFII68 (NTD)-mediated transactivation by v-Src.
The three genes hTAF(II)68, 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 hTAF(II)68, 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 hTAF(II)68 and have investigated the potential effects of cytoplasmic signaling on hTAF(II)68 function. Herein, we find that hTAF(II)68 is phosphorylated on tyrosine residue(s) by ectopic expression of v-Src protein tyrosine kinase in vitro and in vivo. The hTAF(II)68 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 hTAF(II)68-mediated transcriptional activation, whereas deletion mutants of v-Src are unable to exert this effect. In addition, cellular Src activity appears important for hTAF(II)68 function since hTAF(II)68-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 hTAF(II)68 are linked to the cytoplasmic Src signal transduction pathway.
Lee
Hye Jin
HJ
Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul 121-743, South Korea.
Kim
Sol
S
Pelletier
Jerry
J
Kim
Jungho
J
D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D009154:Mutation; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation; D018909:src Homology Domains
C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors; D015688:Oncogene Protein pp60(v-src)