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Human papillomavirus type 16 regulatory protein E2 (HPV16 E2) is a multifunctional viral protein essential for the life cycle of HPV16, the primary etiological agent of cervical cancer [3, 5]. It functions as a sequence-specific DNA-binding protein that regulates viral transcription and initiates DNA replication by recruiting the viral E1 helicase to the origin of replication [4, 9]. Crucially, E2 acts as a transcriptional repressor of the E6 and E7 oncogenes; the loss of E2 expression, typically occurring through viral genome integration into the host chromosome, leads to the overexpression of these oncogenes and subsequent malignant transformation [1, 3, 8]. Beyond its regulatory roles, E2 has been found to possess intrinsic helicase activity and the ability to suppress host innate immune responses by inhibiting interferon signaling pathways [4, 10]. Therapeutic strategies targeting HPV16 E2 include small molecules designed to disrupt the E1-E2 interaction, inhibitors of its DNA-binding domain, and agents like CK2 inhibitors that promote its degradation [7, 11, 14]. Because E2 is present in early-stage infections but often absent in advanced cancers, it serves as both a therapeutic target for preventing progression and a biomarker for assessing viral integration and disease severity [12, 16].
Inhibition of E1-E2 protein-protein interaction, disruption of E2-DNA binding, inhibition of intrinsic E2 helicase activity, and promotion of E2 proteasomal degradation via CK2 inhibition.
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