Skp2, also known as S-phase kinase-associated protein 2, is a crucial member of the ubiquitin-proteasome system (UPS) [1-3]. The UPS is essential for protein degradation, regulating various life processes such as the cell cycle, signal transduction, and DNA repair [1]. As a component of the Skp2-SCF E3 ligase complex, Skp2 conjugates ubiquitin chains to diverse substrates, either inducing proteasome-mediated proteolysis or modulating the function of tagged substrates [2]. It participates in multiple cellular functions like cell proliferation, metabolism, and tumorigenesis by contributing to the ubiquitination and degradation of specific tumor suppressors [3].

Genetic mouse models have demonstrated the oncogenic properties of Skp2. In fusion-negative rhabdomyosarcoma, SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program, affects stemness and tumorigenic features, and prevents in vivo tumor growth [4]. In non-small cell lung cancer cells, knockdown of Skp2 inhibits viability, anchorage-independent growth, and in vivo tumor development [5]. In pancreatic ductal adenocarcinoma, inhibition of the SKP2/PSPC1 axis by a traditional inhibitor of SKP2 impairs the migration of PDAC cells [6].

In conclusion, Skp2 is a key molecule in the UPS, playing a significant role in regulating cellular processes. Model-based research, especially through gene knockout or conditional knockout mouse models, has revealed its oncogenic functions in various cancers. Targeting Skp2 shows promise as a novel strategy for treating cancers and potentially other diseases such as psoriasis [1, 5-7, 9, 10].