Ppp1r13b, also known as ASPP1 (apoptosis stimulating of p53 protein 1), is a major member of the apoptosis-stimulating proteins of the p53 family. It enhances apoptosis by stimulating p53-transactivation of selected proapoptotic target genes and is involved in pathways like the PI3K-Akt signaling pathway [2,4]. It plays a crucial role in maintaining genomic integrity, especially in hematopoietic stem cells (HSCs) [4,5].

In silicosis, SiO₂ downregulates circRNA-012091, leading to upregulation of downstream Ppp1r13B. Transfection experiments in L929 cells show that Ppp1r13B promotes the proliferation and migration of lung fibroblasts through endoplasmic reticulum stress (ERS) and autophagy, which is crucial for the development of pulmonary fibrosis in silicosis [1]. In sheep, oar-miR-485-5p targets Ppp1r13B to regulate myoblast proliferation, and exogenous estradiol supplementation affects the expression of oar-miR-485-5p and Ppp1r13B to promote myoblast proliferation [2]. In chickens, circPPP1R13B promotes skeletal muscle satellite cell proliferation and differentiation by targeting miR-9-5p and activating the IGF/PI3K/AKT signaling pathway [3]. In acute myeloid leukemia (AML), impaired regulation of Ppp1r13B contributes to leukemogenesis and primary therapy resistance, and its mRNA expression patterns define a distinct prognostic profile [4].

In summary, Ppp1r13b is essential for apoptosis regulation and genomic integrity maintenance. Through model-based research, it has been shown to be involved in diseases such as silicosis-related pulmonary fibrosis, muscle-related development in sheep and chickens, and AML. Understanding Ppp1r13b's function provides insights into the mechanisms of these diseases, potentially guiding the development of new therapeutic strategies.

References:

1. Cheng, Yusi, Luo, Wei, Li, Zhuang, Yao, Honghong, Chao, Jie. . CircRNA-012091/PPP1R13B-mediated Lung Fibrotic Response in Silicosis via Endoplasmic Reticulum Stress and Autophagy. In American journal of respiratory cell and molecular biology, 61, 380-391. doi:10.1165/rcmb.2019-0017OC. https://pubmed.ncbi.nlm.nih.gov/30908929/

2. Liu, Siqi, Liu, Ziyi, Wang, Peng, Liu, Yufang, Chu, Mingxing. 2023. Estrogen-mediated oar-miR-485-5p targets PPP1R13B to regulate myoblast proliferation in sheep. In International journal of biological macromolecules, 236, 123987. doi:10.1016/j.ijbiomac.2023.123987. https://pubmed.ncbi.nlm.nih.gov/36906210/

3. Shen, Xiaoxu, Wei, Yuanhang, You, Guishuang, Zhu, Qing, Yin, Huadong. 2021. Circular PPP1R13B RNA Promotes Chicken Skeletal Muscle Satellite Cell Proliferation and Differentiation via Targeting miR-9-5p. In Animals : an open access journal from MDPI, 11, . doi:10.3390/ani11082396. https://pubmed.ncbi.nlm.nih.gov/34438852/

4. Schittenhelm, Marcus M, Kaiser, Max, Győrffy, Balázs, Kampa-Schittenhelm, Kerstin M. 2024. Evaluation of apoptosis stimulating protein of TP53-1 (ASPP1/PPP1R13B) to predict therapy resistance and overall survival in acute myeloid leukemia (AML). In Cell death & disease, 15, 25. doi:10.1038/s41419-023-06372-0. https://pubmed.ncbi.nlm.nih.gov/38195541/

5. Yamashita, Masayuki, Nitta, Eriko, Suda, Toshio. 2015. Regulation of hematopoietic stem cell integrity through p53 and its related factors. In Annals of the New York Academy of Sciences, 1370, 45-54. doi:10.1111/nyas.12986. https://pubmed.ncbi.nlm.nih.gov/26695737/