What is the role of E6 protein in high-risk HPV infection?

The E6 protein of high-risk human papillomavirus (HPV), particularly types 16 and 18, plays a crucial role in the viral pathogenesis leading to cervical and other anogenital cancers. One of its primary mechanisms is the binding and subsequent degradation of the p53 tumor suppressor protein.

p53 is essential for regulating the cell cycle and inducing apoptosis in response to DNA damage. By targeting p53 for degradation, the E6 protein effectively removes the cell's ability to stop the cell cycle in response to DNA damage, allowing cells with potential oncogenic mutations to continue proliferating. This action contributes to the development of malignancies as it skews the delicate balance of cellular control mechanisms that prevent tumorigenesis.

In contrast, while there are several roles that proteins like E7 (another early protein of high-risk HPV) play, including the inhibition of the Rb (retinoblastoma) protein, the direct association of E6 with p53 degradation is one of the hallmark mechanisms of HPV oncogenicity. Therefore, the role of E6 in high-risk HPV infection primarily revolves around its capacity to manipulate cellular pathways to promote uncontrolled cell division, underlining the significance of p53 in the context of tumor suppression.