Core Viewpoint - Targeted protein degradation represents a significant advancement in treating diseases previously deemed untreatable, particularly for traditionally "undruggable" targets such as transcription factors and scaffold proteins [2][6]. Group 1: Development of New Screening Methods - A novel high-throughput screening platform named DEFUSE (DE ath FUS ion E scaper) has been developed to identify small molecule protein degraders, enabling efficient degradation of oncoprotein SKP2 [3][10]. - The DEFUSE platform utilizes a fusion of target proteins with a rapidly activated death protein, allowing for a visual representation of cell survival or death based on the presence of degradation compounds [6][8]. Group 2: Discovery of New Degraders - The research team identified a small molecule, SKPer1, which specifically promotes the degradation of the oncogenic protein SKP2 and selectively kills SKP2-expressing cancer cells [8][10]. - SKPer1 functions as a novel molecular glue degrader, recruiting SKP2 to the ubiquitin ligase STUB 1, facilitating its ubiquitination and subsequent degradation [8][10]. Group 3: Implications for Cancer Treatment - SKPer1 demonstrated significant tumor-suppressive effects in vivo and exhibited good safety profiles, indicating its potential as a therapeutic agent [10]. - The study suggests that a 10-amino acid sequence derived from SKP2 can serve as a universal degradation tag, allowing other target proteins fused with this tag to be recruited for degradation by SKPer1 [10].