Hypoxic conditions prompt internal ribosome entry site (IRES)-mediated translation of some of the hallmark cancer genes, such as VEGF. This translational switch is extremely vital for cell survival and tumor progression. Heterogeneity in ribosomes due to the diversity of ribosomal RNA (rRNA) and protein composition has been postulated to generate ‘specialized ribosomes’ that differentially regulate translation. A VEGF IRES sequence was used as bait to identify unique proteins bound at the IRES in breast cancer cells grown in hypoxia.