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The role of the Tumor Suppressor ING1b in Cell Cycle Progression

Marco Garate, MD, B.C. Cancer Agency, Vancouver, BC.

The tumor suppressor ING1b plays an important role in cellular stress response. We have previously shown that UV irradiation induces ING1b expression in melanoma cell lines enhancing DNA repair. Recently, we have shown that DNA-damage induces a rapid phosphorylation of ING1b in melanoma cells and we identified the residue S126 as the one phosphorylated upon this stress. Furthermore, we observed that the overexpression of ING1b reduces the levels of cyclin B1 in a Ser126 phosphorylation-dependent fashion. Because cyclin B1 is essential for the entry into mitosis and cell proliferation, our results suggested that ING1b may play a key role in cell cycle regulation. Consistently, ING1b expression decreased cell proliferation and this effect was also dependent of Ser126 phosphorylation. Besides, a recent report described that a 14-3-3 protein can translocate ING1b to the cytosol, impairing its ability to arrest cells through upregulation of the tumor suppressor p21Waf1. Based on these evidences, we hypothesize that regulation of ING1b expression associated to its phosphorylation induces cell cycle arrest and inhibits cell progression in melanoma cells. Combining molecular biology and cell cycle approaches we propose to determine the role of ING1b in cell cycle progression. Therefore, this work will contribute to unveil the molecular mechanism of how tumor suppressors control cell cycle and in particular in the design of better therapies to treat melanoma patients targeting events that define the fate of normal and malignant cells.

©2007