Inhibitor of apoptosis-stimulating protein of p53 mRNA (PPP1R13L) (iASPP mRNA)

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) mRNA, transcribed from the PPP1R13L gene, is a critical negative regulator of the p53 tumor suppressor family (p53, p63, and p73). The iASPP protein encoded by this mRNA binds directly to the DNA-binding domain of p53, preventing the activation of pro-apoptotic genes such as BAX and PUMA (Bergamaschi et al., 2003; UniProt Q8WUF5). In many human cancers, iASPP mRNA is significantly overexpressed, which correlates with poor clinical outcomes, advanced tumor stage, and resistance to chemotherapy (Sullivan & Lu, 2007; Chen et al., 2010). As a therapeutic target, iASPP mRNA is primarily targeted using RNA-based strategies, including small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), designed to knockdown its expression and thereby sensitize cancer cells to apoptosis (Notari et al., 2011). Beyond its oncogenic role, iASPP is involved in maintaining epithelial integrity and modulating NF-kappaB-mediated inflammatory responses. While therapeutic development is currently in the preclinical stage, targeting iASPP mRNA represents a promising approach for treating p53-wildtype tumors and overcoming chemoresistance in various malignancies.

Other names

PPP1R13L mRNARelatively abundant in islets mRNARAI mRNANF-kappa-B-interacting protein mRNANKIP mRNAASPP3 mRNA

RNA interference-mediated gene silencing or RNase H-mediated mRNA degradation to reduce iASPP protein expression and restore p53-dependent apoptosis.