Ppp1r13l-flox Mouse

Ppp1r13l, also known as inhibitor of apoptosis-stimulating protein of p53 (iASPP), is a conserved inhibitor of p53, selectively regulating a subset of p53 target genes. It is involved in multiple biological processes, including apoptosis, regulation of desmosomes, and inflammatory pathways [1,2].

In cervical cancer, PPP1R13L promotes cell proliferation, epithelial-mesenchymal transition, cycle progression, and glycolysis via the PTEN/AKT/mTOR pathway. It regulates the transcription of PTEN through its Ank-SH3 domain interaction with p53 family members, p53 and p63 [1].

In the context of paediatric dilated cardiomyopathy, biallelic variants in PPP1R13L have been identified in multiple children. The protein encoded by PPP1R13L, iASPP, acts as a regulator of desmosomes and is implicated in inflammatory pathways, and its deficiency leads to progressive DCM, often resulting in death or transplant [2].

In lung adenocarcinoma, PPP1R13L, as an oncoprotein, along with transcription factor SP1, forms a feedback loop to regulate nicotine-induced epithelial-mesenchymal transition [3]. High iASPP (PPP1R13L) expression in acute myeloid leukemia (AML) is an independent predictor of adverse clinical outcome, and its attenuation reduces leukemic blast proliferation and increases apoptosis susceptibility [4].

In summary, Ppp1r13l plays crucial roles in various biological processes and disease conditions. In cancer, it can promote cancer progression, such as in cervical and lung cancers, and is related to adverse outcomes in AML. In cardiomyopathies, biallelic variants in Ppp1r13l are associated with severe paediatric dilated cardiomyopathy and arrhythmogenic cardiomyopathy. The study of Ppp1r13l using genetic models helps to understand its functions in these disease areas and may provide potential therapeutic targets.