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closeYB1 or NF-Y?
Posted by mantor on 28 Dec 2011 at 15:30 GMT
The logic of the paper flows well untill the Authors analyze the transcription factors mediating the MEK/ERk effects. The TFBS analysis on TRANSFAC indicates E2Fs and NF-Y sites as enriched. This fits well with the recent bioinformatic data indicating that the two are very often partners in genes overexpressed in tumors (Tavazoie et al., Mol Cell 36, 900, 2009; Gatta et al., Cell Death Dis. 2, e162, 2011). Thereafter, they bring in the analysis YB1. There is a reason why the site is called NF-Y: it is bound with great specificity by NF-Y (Dolfini et al., Cell Cycle 8, 4127, 2009). YB1, originally identified in an expression screening with a Y-box oligo (an inverted CCAAT box), has never been shown to have the exquisite specificty of NF-Y for the CCAAT -or NF-Y- matrix present in TRASNFAC and Jaspar, to the best of my knowlege. Indeed, YB1 has been shown to partake in aspects other than primary mRNA production, as it is the case for NF-Y, including translational control. Specifically the Cyclin B1 system is a classic NF-Y target (Imbriano et al., BBA Rev Cancer 1825: 131, 2011). Which is confirmned by the Authros' data, actually. YB1 does have a role in advanced stages of tumors, so I don't have a problem with the last part of the work, but that might be completely indepentent from the original NFY site identified in the expression screening. The reader is left with the impression that YB1 is the mediator of the NFY site activity, protein-wise. Which is likely not the case. In fact, recent ChIP-Seq analysis with JNKs has identifed the NF-Y site as mediator of DNA association: a precise overlap with NF-Y locations was determined also by ChIP-Seq with NF-YA (Tiwari et al. Nature Genetics 44: 94, 2011). In conclusion, I have a feeling that the data further support the model whereby NF-Y, alone or with other TFs such as E2Fs, mediates signalling of this clesses of kinases.