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

Abstract

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.

Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer

“…YBX1 functions as both a DNA and RNA binding protein and has been implicated in numerous cellular processes, including regulation of transcription and translation, premRNA splicing, DNA reparation, and mRNA packaging (36). YBX1 activation has been associated with cancer progression (37,38), the epithelial-mesenchymal transition (39), metastasis (40), and drug resistance (41,42). Western blot with a specific antibody confirmed that YBX1 is enriched in the TP53TG1 pull-down (Fig.…”

CONSTANS Imparts DNA Sequence Specificity to the Histone Fold NF-YB/NF-YC Dimer

“…The sequence targeted by NF-Y [RRCCAAT(C/G)(A/G)] has long been known, thanks to numerous biochemical and genomic studies performed in mammals (Dolfini et al, 2009;Dolfini and Mantovani, 2013). By examining the NF-CO matrices ( Figures 2C and 3), one can notice a clear similarity to the NF-Y CCAAT matrix, RRCCAAT(C/G)(A/G), with a deviation of two nucleotides (underlined).…”

Transforming Growth Factor β1 (TGF-β1) Enhances Expression of Profibrotic Genes through a Novel Signaling Cascade and MicroRNAs in Renal Mesangial Cells

“…This CCAAT motif is one of the most common cis-acting elements in the promoter and enhancer region of a large number of eukaryotic genes (47). Furthermore, this specific motif has been shown to be enriched in several genes overexpressed in a variety of cancers, including breast, colon, thyroid, prostate, and leukemia (48). However, its role in DN is not known.…”

“…Previously, our group demonstrated that miR-216a is induced by TGF-␤1 and mediates TGF-␤1-induced Akt kinase activation and collagen expression in MMC by targeting Ybx1 and Pten (49,50). Because Ybx1 also recognizes Y-box (CCAAT) (48), it is possible that the decrease of RIK and miR-130b is caused by miR216a-mediated down-regulation of Ybx1 (49) (Fig. 7).…”