Nuclear colocalization and complex formation of insulin with retinoblastoma protein in HepG2 human hepatoma cells

Previous structural and biochemical evidence had suggested that insulin may bind to the nuclear tumor suppressor retinoblastoma protein (RB). The pres ent study is now the first to unravel the physical and functional interacti on between a growth factor and an anti-oncoprotein, specifically demonstrat ing the association between insulin and RE in living cells and finding that this complex formation is relevant for cell division Our immunofluorescenc e microscopy data suggest that insulin colocalizes with RE in the cell nucl ei of HepG2 human hepatoma cells and that it contacts the B-region of the R E pocket. Furthermore, these events were found to correlate with an enhance ment of cell proliferation. These results are in line with the initial stru cture-based predictions and, moreover, provide a suitable starting point fo r the further understanding as well as the pharmacological modulation of nu cleocrine interactions between growth factors and tumor suppressors, in phy siology and disease.