title: Stimulation of hTAFII68 (NTD)-mediated transactivation by v-Src.
abstract: 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.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul 121-743, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Jungho
authors.initials: J
authors.lastname: Kim
mesh_terms: 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
chemical_list: C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors; D015688:Oncogene Protein pp60(v-src)