The YEATS domain of Taf14 in Saccharomyces cerevisiae has a negative impact on cell growth

The role of a highly conserved YEATS protein motif is explored in the context of the Taf14 protein of Saccharomyces cerevisiae. In S. cerevisiae, Taf14 is a protein physically associated with many critical multisubunit complexes including the general transcription factors TFIID and TFIIF, the chromatin remodeling complexes SWI/SNF, Ino80 and RSC, Mediator and the histone modification enzyme NuA3. Taf14 is a member of the YEATS superfamily, conserved from bacteria to eukaryotes and thought to have a transcription stimulatory activity. However, besides its ubiquitous presence and its links with transcription, little is known about Taf14’s role in the nucleus. We use structure–function and mutational analysis to study the function of Taf14 and its well conserved N-terminal YEATS domain. We show here that the YEATS domain is not necessary for Taf14’s association with these transcription and chromatin remodeling complexes, and that its presence in these complexes is dependent only on its C-terminal domain. Our results also indicate that Taf14’s YEATS domain is not necessary for complementing the synthetic lethality between TAF14 and the general transcription factor TFIIS (encoded by DST1). Furthermore, we present evidence that the YEATS domain of Taf14 has a negative impact on cell growth: its absence enables cells to grow better than wild-type cells under stress conditions, like the microtubule destabilizing drug benomyl. Moreover, cells expressing solely the YEATS domain grow worser than cells expressing any other Taf14 construct tested, including the deletion mutant. Thus, this highly conserved domain should be considered part of a negative regulatory loop in cell growth

Quantitating whole lesion tumor biology in rectal cancer MRI: taking a lesson from FDG-PET tumor metrics

PURPOSE To determine the value of novel whole tumor metrics in DWI-MRI and DCE-MRI of rectal cancer treatment assessment. MATERIALS AND METHODS This retrospective study included 24 uniformly treated patients with rectal adenocarcinoma who underwent MRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after chemoradiotherapy. Two experienced readers independently measured tumor volume and apparent diffusion coefficient (ADC) on DWI-MRI and tumor volume and transfer constant K on DCE-MRI. In addition, we explored and defined Total Lesion Diffusion (TLD) as Total DWI tumor volume multiplied by mean volumetric ADC and Total Lesion Perfusion (TLP) as the total DCE tumor volume multiplied by the mean volumetric K . These metrics were correlated with histopathologic percent tumor regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). RESULTS For both readers, post-treatment TLP revealed comparable correlations with %TR compared with K (reader 1; Spearman's rho = - 0.36 vs. - 0.32, reader 2; Spearman's rho = - 0.32 vs. - 0.28). In addition, TLP afforded the highest inter-reader agreement at post-treatment among TLP, DCE vol, and K (CCC: 0.64 vs. 0.36 vs. 0.35). Post-treatment TLD showed similar correlation with %TR as DWI volume in reader 1 and superior correlation with %TR for reader 2 (reader 1; Spearman's rho - 0.56 vs. - 0.57, reader 2; Spearman's rho - 0.59 vs. - 0.45). CONCLUSION The novel tumor metrics TLD and TLP revealed similar results to established metrics for correlation with tumor response with equivalent or superior inter-reader agreements and we recommend that these be studied in larger trials