Fig. 3.

STAT-5-dependent activation of ATM and ATR pathways, required for HPV genome amplification

High-risk HPV activates STAT-5 to mediate TopBP1 transcriptionally to promote ATR pathway. Meanwhile, STAT-5 does not directly regulate Tip60; instead, it partially work through PPARg to manipulate Tip60 activation which consequently facilitates ATM activation. HPV E7 oncogene is responsible for STAT-5 activation as well as interaction with other factors such as Rb, ATM, NBS1, HDAC, and p21. E6 gene may collaborate with other viral proteins to act on Tip60 in addition to its role in p53 degradation. E2 is capable of interacting with TopBP1 to mediate HPV initial replication