The topo II inhibition exerted by dexrazoxane is due to its binding and stabilisation of the protein/DNA complex.
The binding of Wnt to Fz leads to dephosphorylation and stabilisation of β-catenin, enabling it to be translocated into the nucleus, where it interacts with members of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family of transcription factors to stimulate the expression of target genes.
Nutlins penetrated cell membranes and inhibited p53 MDM2 binding, leading to stabilisation of p53 and activation of p53 target genes (Stommel and Wahl, 2004; Vassilev et al, 2004).
Hypoxia interrupts this process and leads to its stabilisation, nuclear translocation and binding to its dimerisation partner HIF-1ß (Wenger, 2002).
The mechanism could be due to direct binding to folding intermediates [ 51], allowing stabilisation prior to correct folding and inhibition of aggregate formation.
Peptide binding to MHC molecules was monitored by stabilisation assays, in which TAP-deficient, HHD-transfected RMA-S cells (RMA-S/HHD) are loaded with a peptide, and HHD expression on the cell surface is monitored by FACS.
Wnt binding to frizzled receptors leads to the cytosolic stabilisation and accumulation of β-catenin, which translocates to the nucleus and forms a complex with T-cell factor transcription factors, thereby regulating target gene expression.
Previous studies have shown that binding of tamoxifen to ER α leads to stabilisation, whereas binding to ICI182780 leads to degradation of ER α without activation (Ali et al, 1993).
Notably, MMP-9 requires stabilisation by binding to neutrophil gelatinase-associated lipocalin (NGAL), which is reportedly increased in bile in patients suffering from malignant pancreatobiliary obstruction (Zabron et al., 2011).
These results suggest that HuR contributes to the stabilisation of VEGF-A and COX-2 mRNAs by binding to these mRNAs.
