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

Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a key member of the ASPP family that functions as a major negative regulator of the p53 tumor suppressor protein (UniProt Q8WUF5) [1]. It specifically binds to the DNA-binding domain of p53, preventing the activation of pro-apoptotic target genes such as BAX and PUMA, thereby promoting cell survival (Bergamaschi et al., 2003) [2]. iASPP is frequently overexpressed in various human cancers, including breast, lung, and leukemia, where it correlates with poor prognosis and resistance to therapy (Sullivan and Lu, 2007) [3]. Beyond its role in apoptosis, iASPP also regulates NF-kappaB signaling and is involved in cardiac development and spermatogenesis (Notari et al., 2011) [4]. Therapeutic strategies targeting iASPP aim to disrupt its interaction with p53 using small molecules or peptides to restore p53-mediated apoptosis in cancer cells (Lu et al., 2015) [5]. However, targeting iASPP presents challenges due to its essential role in maintaining cardiac integrity, as evidenced by the development of cardiomyopathy in iASPP-deficient models [4].

Other names

PPP1R13LRelA-associated inhibitorRAIProtein phosphatase 1 regulatory subunit 13-likeNKIP1

Disruption of the protein-protein interaction between iASPP and the DNA-binding domain of p53, thereby releasing p53 to induce the transcription of pro-apoptotic genes like BAX and PUMA.