S-phase kinase-associated protein 2 messenger RNA (SKP2 mRNA)

S-phase kinase-associated protein 2 (Skp2) mRNA encodes the substrate-recognition component of the SCFSkp2 E3 ubiquitin ligase complex, which serves as a master regulator of the eukaryotic cell cycle (UniProt: P63272). The primary function of the encoded Skp2 protein is to facilitate the polyubiquitination and subsequent proteasomal degradation of cyclin-dependent kinase inhibitors, most notably p27Kip1, thereby promoting the transition from G1 to S phase (PubMed: 20837501). In many human malignancies, Skp2 mRNA is significantly overexpressed, leading to the depletion of tumor suppressors and driving uncontrolled cellular proliferation and survival (PubMed: 15622179). Consequently, Skp2 mRNA has emerged as a viable therapeutic target, where its downregulation via antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) can restore p27Kip1 levels and induce cell cycle arrest or apoptosis in malignant cells (PubMed: 12140755). While small molecule inhibitors targeting the Skp2 protein-protein interactions are also under investigation, RNA-targeted strategies offer high specificity for the transcript itself. However, the clinical development of therapies targeting Skp2 mRNA faces hurdles such as the requirement for efficient delivery systems and the potential for affecting normal hematopoietic or epithelial cell turnover.

Other names

FBXL1 mRNAF-box protein Skp2 mRNAp45 mRNAS-phase kinase-associated protein 2 (p45) mRNAFBX22 mRNA

RNA interference (siRNA) or RNase H-mediated degradation (ASO) of the Skp2 transcript, leading to reduced translation of the Skp2 protein and subsequent stabilization of its tumor-suppressive substrates like p27Kip1 (PubMed: 12140755, 15622179).