Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

The Y box is an important sequence motif found in promoters and enhancers containing a CCAAT box - one of the few elements enriched in promoters of large sets of genes overexpressed in cancer. The search for the transcription factor(s) acting on it led to the biochemical purification of the nuclear factor Y (NF-Y) heterotrimer, and to the cloning - through the screening of expression libraries - of Y box-binding protein 1 (YB-1), an oncogene, overexpressed in aggressive tumors and associated with drug resistance. These two factors have been associated with Y/CCAAT-dependent activation of numerous growth-related genes, notably multidrug resistance protein 1. We review two decades of data indicating that NF-Y ultimately acts on Y/CCAAT in cancer cells, a notion recently confirmed by genome-wide data. Other features of YB-1, such as post-transcriptional control of mRNA biology, render it important in cancer biology.