期刊
VIRUSES-BASEL
卷 14, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/v14081681
关键词
HPV E7; protein kinase CK2 inhibitor; CIGB-300; pRB
类别
资金
- ICGEB Arturo Falaschi Fellowship [IG 2019-ID.23572]
- Associazione Italiana per la Ricerca sul Cancro
This study investigated the physical interaction of CIGB-300 with HPV-E7 and its impact on CK2-mediated phosphorylation. The findings revealed that CIGB-300 binds to the N terminal region of E7 proteins of the HPV-16 type, reducing CK2-mediated phosphorylation of E7 and its binding to pRB. However, targeting of E7 phosphorylation by CIGB-300 seems to be dispensable for inducing cell death in HPV-18 cervical cancer-derived cells.
CIGB-300 is a clinical-grade anti-Protein Kinase CK2 peptide, binding both its substrate's phospho-acceptor site and the CK2 alpha catalytic subunit. The cyclic p15 inhibitory domain of CIGB-300 was initially selected in a phage display library screen for its ability to bind the CK2 phospho-acceptor domain ofHPV-16 E7. However, the actual role of this targeting in CIGB-300 antitumoral mechanism remains unexplored. Here, we investigated the physical interaction of CIGB-300 with HPV-E7 and its impact on CK2-mediated phosphorylation. Hence, we studied the relevance of targeting E7 phosphorylation for the cytotoxic effect induced by CIGB-300. Finally, co-immunoprecipitation experiments followed by western blotting were performed to study the impact of the peptide on the E7-pRB interaction. Interestingly, we found a clear binding of CIGB-300 to the N terminal region of E7 proteins of the HPV-16 type. Accordingly, the in vivo physical interaction of the peptide with HPV-16 E7 reduced CK2-mediated phosphorylation of E7, as well as its binding to the tumor suppressor pRB. However, the targeting of E7 phosphorylation by CIGB-300 seemed to be dispensable for the induction of cell death in HPV-18 cervical cancer-derived C4-1 cells. These findings unveil novel molecular clues to the means by which CIGB-300 triggers cell death in cervical cancer cells.
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