Method and Kit for Evaluating Transformed Cells
Summary Human papillomaviruses (HPV's) are small DNA viruses of the papovavirus family that infect human epithelial cells. “Low risk†HPV’s can cause benign hyperplasia’s such as genital warts, while “high risk†HPV’s, e.g., HPV-16 and HPV-18 can cause carcinomas such as cervical or penile carcinoma. Two HPV encoded proteins, E6 and E7, known as viral oncoproteins are consistently expressed in the cancers and lead to transformation of infected cells. The transforming functions of the papillomaviruses reflect their ability to interfere with control mechansims that govern the normal program of cellular growth and differentiation.The HPV E6 oncoprotein interacts with the nuclear phosphoprotein p53 which is believed to act as a tumor suppressor in its native state by functioning as a key mediator of DNA repair. The HPV E7 oncoprotein has been shown to interact with p21Cip1 and overcomes p21Cip1 inhibition of the kinase activity of cyclin/cdk complexes. p21Cip1 has been recognized as a major mediator of the p53 suppressor protein. Increased levels of p53, as a response to a cellular challenge such as DNA damage, enhance the synthesis of p21Cip1. As a direct consequence of the higher p21Cip1 levels, the enzymatic activity of cyclin dependent kinases is decreased and the cell undergoes a specific cell cycle arrest.
Applications The invention relates to the identification of compounds capable of inhibiting dysregulated cellular proliferation and/or differentiation caused by human papillomaviruses.
This invention has broad assay/diagnostic potential for use in determining the extent of interaction and/or inactivation between a cyclin/cdk inhibitor and the HPV E7 oncoprotein and thus for evaluating the proliferative state of a transformed cell. The invention may also be used to identify therapeutic compounds capable of inhibiting the interaction between a cyclin/cdk inhibitor and HPV E7, as well as compounds capable of inhibiting growth of an HPV-associated cancer cell. For Further Information Please Contact the Director of Business Development Michal Preminger Email: [email protected] Telephone: (617) 432-0920
Inventor(s): Munger, Karl
Type of Offer: Licensing
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