PMC:441373 / 38785-41674 JSONTXT

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However, over the process of evolutionary time, with the acquisition of new domains and duplication of the chordate TACC precursor, the chordate TACC proteins have acquired the ability to directly interact with some of the other components of these complexes (such as the LSm proteins, nuclear hormone receptors, GAS41, accessory proteins and transcription factors), and thus evolved additional functions within these complexes. Indeed, the first assigned function of a vertebrate TACC protein, mouse TACC3, was as a transcriptional coactivator of the ARNT mediated transcriptional response to hypoxia and polyaromatic hydrocarbons [7]. Mouse TACC3 has also been reported to interact with the transcription factor STAT5 [33]. Recently, we have demonstrated that TACC2 and TACC3 can bind to nuclear histone acetyltransferases [34], further confirming a more direct role for the TACC proteins in transcriptional and chromatin remodeling events. Interestingly although all human TACC proteins can directly interact with the histone acetyltransferase pCAF in vitro, the TACC1 isoforms expressed in human breast cancer cells do not interact with this histone acetylase [34]. This may be attributable to the proposed function of the Exon 1 containing TACC1 variants in RNA processing, via the interaction with LSm-7 and SmG [19]. Thus, alternative splicing of the TACC1 gene adds further diversity to TACC1 function, as the deletion of specific exons and their associated binding domains will change the potential protein complexes with which they can associate, either directly, or by redirecting the splice variants to different subcellular compartments. With the duplication of the TACC1/TACC2 ancestor, it is apparent that an even greater functional diversity may have been introduced into the TACC family. The TACC2 protein retains the ability of TACC3 to interact with GAS41, INI1, histone acetyltransferases and transcription factors (in this case, RXRβ) (Fig. 7) [3,34]. However, the tissue specific splicing of the 5 kb exon in the TACC2l isoform [3] indicates that this protein has several temporal and tissue specific functions yet to be 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