Degradation of tumour suppressor ING3: Pathway and its role in cell cycle progression

Cutaneous malignant melanoma is a life-threatening skin cancer that is very resistant to conventional radio- and chemotherapy and has a low survival rate. Thus, it is important to understand the molecular changes underlying the onset and progression of the disease. The novel tumour suppressor ING3 acts to inhibit cell growth. A number of previous studies have demonstrated that ING3 switches on and off during normal cell division, and that it enhances cell death in melanoma cells when they are exposed to UV-light. Dr. Guangdi Chen has identified that the expression of ING3 degrades (or decreases) much faster in melanoma cells than in regular melanocytes (healthy melanin-producing cells) during the cell cycle. This rapid degradation may be an important cause of aberrant ING3 expression and the loss of its tumour suppressing function. However, the mechanism of ING3 protein degradation and its role in cell cycle progression remain unclear. Chen is investigating the pathway of ING3 protein degradation and assessing its role in cell cycle progression. By understanding the molecular mechanisms of ING3 tumour suppressive functions in cell cycle progression, he hopes his work could help in the design of novel strategies for cancer prevention and treatment. Chen’s post-doctoral fellowship is jointly funded by MSFHR and the VGH & UBC Hospital Foundation.