Epstein-Barr virus(EBV)and human papillomavirus(HPV)infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma,respectively.However,clinical analyses demonstrate that EBV or HPV is associated wi...Epstein-Barr virus(EBV)and human papillomavirus(HPV)infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma,respectively.However,clinical analyses demonstrate that EBV or HPV is associated with improved response of patients,although underlying mechanism remains unclear.Here,we reported that the oncoproteins of DNA viruses,such as LMP1 of EBV and E7 of HPV,inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif.Inhibition of PERK led to increased level of reactive oxygen species(ROS)that promoted tumor and enhanced the efficacy of chemotherapy in vivo.Consistently,disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models.Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.展开更多
基金This work was funded by the following grants and associations:National Natural Science Foundations of China(81530084 and 81702721)Hunan province natural science funds for Yong scholars(2018JJ3816).
文摘Epstein-Barr virus(EBV)and human papillomavirus(HPV)infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma,respectively.However,clinical analyses demonstrate that EBV or HPV is associated with improved response of patients,although underlying mechanism remains unclear.Here,we reported that the oncoproteins of DNA viruses,such as LMP1 of EBV and E7 of HPV,inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif.Inhibition of PERK led to increased level of reactive oxygen species(ROS)that promoted tumor and enhanced the efficacy of chemotherapy in vivo.Consistently,disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models.Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.
