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Marco Garate, PhD, B.C. Cancer Agency, Vancouver, BC. The enzymes NQO1 and NQO2 play a prominent role in maintaining the cellular equilibrium. NQO1 and NQO2, are present in all tissue types and induced along with a battery of defensive genes in response to stimulus such as oxidants, ultraviolet light, ionizing radiation or chemical compounds. The coordinated induction of these genes provides protection for cells against events such as oxidative stress, and tumor formation. It has been recently shown that NQO1 and NQO2 interact and regulate the stability of the tumor suppressor p53. NQO1 and NQO2 inhibit the degradation of p53 and modulate the p53-dependent programmed cell death. More recently, we discovered that another tumor suppressor, ING1b, shares this mechanism of stabilization with p53. We have further demonstrated that the stabilization that NQO1 exerts on ING1b is dependent on the phosphorylation at the residue serine 126 and abolishment of ING1b phosphorylation shortens life span of this protein. Since NQO1 and NQO2 stabilize proteins which define the fate of normal and malignant cells and the fact that knowledge of the effect of these enzymes in melanoma is lacking, we propose to study the role of NQO1 and NQO1 in the progression of malignant melanoma. Peer-Reviewed Publications Supported by the Canadian Dermatology Foundation ©2008 |
