N-Degron-Based PROTAC Targeting PLK1: A Potential Therapeutic Strategy for Cervical Cancer.

ABSTRACT: Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability wit

SUBMITTER: Gunasekaran P 

PROVIDER: S-EPMC12389170 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature