Biology subjects

Basukala, O.

Publications and source records attributed to Basukala, O..

2 recordsLinked to original sources

bioRxiv2026

CKII-Phosphorylated HPV-16 E7 Disrupts Planar Cell Polarity by Recruiting Vangl1

High-risk human papillomaviruses (HPVs) depend on continuous expression of the E6 and E7 oncoproteins to sustain malignant transformation. The high-risk E7 oncoprotein is multifunctional, and its phosphorylation by Casein Kinase II (CKII) amplifies its oncogenic potential. Here, we identify Vangl1, a core planar cell polarity (PCP) scaffold protein, as a novel, phosphorylation-dependent interactor of HPV-16 E7. CKII-mediated phosphorylation is required for Vangl1 recruitment, and this interaction is largely selective for HPV-16 E7. In cervical cancer cells, E7 expression profoundly disrupts Vangl1 homeostasis, producing a biphasic proteostatic imbalance in which phosphorylated Vangl1 is aberrantly retained. This retention parallels E7 stability, revealing a reciprocal oncogenic stabilization. E7 also impairs Vangl1 trafficking and localization by co-opting the clathrin adaptor subunit AP1M1. Functionally, Vangl1 depletion mirrors E6/E7 loss in CaSki spheroids by disrupting spheroid architecture, reducing invasiveness, and increasing chemosensitivity. Taken together, these findings position Vangl1 as a central effector in E7-mediated cervical transformation and invasive progression. TeaserE7s control of Vangl1 reveals a polarity-remodeling mechanism that drives cervical cancer invasion and progression.

cancer biology↗

bioRxiv2022

CIGB-300 peptide targets the CK2 phospho-acceptor domain on Human Papillomavirus E7 and disrupts the Retinoblastoma (RB) complex in cervical cancer cells

CIGB-300 is a clinical-grade anti- Protein Kinase CK2 peptide, binding both its substrates phospho-acceptor site and the CK2 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 of HPV-16 E7. However, the actual role of this targeting in CIGB-300s 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 blot 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 from HPV-16 type. Accordingly, the in vivo physical interaction of the peptide with HPV-16 E7 reduces the CK2-mediated phosphorylation of E7, as well as its binding to the tumour 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 the CIGB-300 triggers cell death in cervical cancer cells.

cancer biology↗