PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis

Significance Human papillomaviruses (HPV) uncouple proliferation from differentiation to enable virus replication in epithelial cells. HPV E7 proteins are well established to promote proliferation by binding to and inactivating retinoblastoma family proteins and other cell cycle inhibitors. However, mechanisms by which high-risk HPV oncoproteins inhibit differentiation have not been defined. This paper identifies a mechanism by which high-risk HPV E7 inhibit keratinocyte differentiation. The inhibition of differentiation requires degradation of the cellular protein PTPN14 by high-risk HPV E7, and this degradation is related to the ability of high-risk HPV oncoproteins to immortalize keratinocytes and to cause cancer.