Disease relevance of TAF15

• Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma [1].
• An in vitro enzymatic assay coupled to proteomics analysis reveals a new DNA processing activity for Ewing sarcoma and TAF(II)68 proteins [2].

High impact information on TAF15

• Moreover, we demonstrate that hTAF(II)68 co-purifies also with the human RNA polymerase II and can enter the preinitiation complex together with Pol II [3].
• Here we report the cloning and characterization of a novel human TBP-associated factor, hTAF(II)68 [3].
• Moreover, EWS is not exclusively associated with TFIID but, similarly to hTAFII68, is also associated with the Pol II complex [4].
• Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by recurrent t(9;22) or t(9;17) translocations resulting in fusions of the NH2-terminal transactivation domains of EWS or TAF2N to the entire TEC protein [5].
• We demonstrate that the N-terminus of TAFII68 efficiently stimulates transcription when fused to two different DNA binding domains and that overexpression of TAFII68-FLI-1 chimeras in NIH3T3 cells leads to oncogenic transformation [6].

Biological context of TAF15

• Investigating the multiple functions of TLS, EWS and TAF15 will enhance our understanding of gene expression as a whole, and also allow us to better understand how these proteins may be contributing to the oncogenic pathways the associated fusion proteins initiate [7].
• We have determined that the translocation results in the fusion of the entire coding region of CHN to the N-terminal transactivation domain of RBP56/hTAFII68 [1].
• The RBP56/hTAFII68 gene spans about 37kb and consists of 16 exons from 33bp to 562bp [8].
• The RBP56 gene was mapped to chromosome 17q11.2 to q12 [9].
• Taken together, our results suggest that the biological activities of hTAF(II)68 are linked to the cytoplasmic Src signal transduction pathway [10].

Associations of TAF15 with chemical compounds

• 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 [10].
• The predicted amino acid sequences of RBP56 protein have a serine-, tyrosine-, glutamine-, and glycine-rich region in the N-terminal region, an RNA binding domain and a C2C2 finger motif in the central region, and degenerate repeats of DR(S)GG(G)-YGG sequences in the C-terminal region [9].
• The exchange of the EWS NH2-terminal part with the TAF2N NH2-terminal part in EMC further underscores the oncogenic potential of these protein domains as partners in fusion genes [11].

Other interactions of TAF15

• In the present study, we address the question whether EWS and hTAF(II)68 also display pairing on membrane activities, and to a larger extent whether other proteins also exhibit such activity [2].
• One such multifunctional family is made up of the RNA-binding proteins TLS, EWS and TAF15 [7].
• Molecular cloning of the translocations t(12;22)(p13;q12) and t(12;17)(p13;q11) in acute leukaemia showed that either EWSR1 or its homologue TAF15 are fused to the transcription factor CIZ [12].
• The hTAF(II)68 protein can associated with the SH3 domains of several cell signaling proteins, including v-Src protein tyrosine kinase [10].
• The subunits of Pol II that interact with EWS and hTAFII68 have been identified, confirming the association with the polymerase [4].

Analytical, diagnostic and therapeutic context of TAF15

• By genomic XL PCR and sequence analyses, the breakpoints from 14 cases were mapped in the EWS, RBP56, and CHN genes [13].

References