Anp32e, also known as Acidic leucine-rich nuclear phosphoprotein 32 family member e, is a histone chaperone that removes H2A.Z from chromatin. It belongs to the superfamily of leucine-rich repeat (LRR) proteins and the Acidic Nuclear Phosphoprotein 32 (ANP32) family of protein phosphatase 2 (PPP2) inhibitors [4]. Anp32e is involved in multiple cellular processes such as cell proliferation, apoptosis, and differentiation. It plays a crucial role in early mammalian development, and its dysregulation is associated with various diseases [1,2]. Genetic models, like gene knockout models, have been instrumental in studying its functions.

In the context of renal interstitial fibrosis (RIF), Anp32e was highly expressed in the RIF region of patients with IgA nephropathy, UUO mouse kidneys, and TGF-β1-treated BUMPT cells. Overexpression of Anp32e enhanced the TGF-β1-induced production of fibrosis-related proteins in BUMPT cells, while its knockdown in UUO mice and TGF-β1-stimulated BUMPT cells suppressed the deposition of these proteins. Anp32e overexpression alone could also induce the deposition of these proteins. It was found that Anp32e promoted the deposition of fibrosis-related proteins by regulating the TGF-β1/Smad3 pathway [1]. In gastric cancer, knockdown of Anp32e inhibited cell proliferation and colony formation and induced apoptosis, while overexpression promoted malignancy. Anp32e was positively associated with NUF2 expression, and it promoted tumor cell proliferation and inhibited apoptosis by increasing NUF2 expression [2]. In esophageal cancer, ANP32E knockdown inhibited tumor progression and migration, and enhanced cell sensitivity to paclitaxel. ANP32E regulated EC progression and ferroptosis via the p53/SLC7A11 axis [3].

In conclusion, Anp32e has diverse functions in different biological processes and disease conditions. Gene knockout or knockdown models have revealed its role in promoting fibrosis in the kidneys, cancer progression in the stomach and esophagus. Understanding Anp32e's functions provides insights into the mechanisms of these diseases, potentially leading to new therapeutic strategies.

References:

1. Wei, Ju, Shan, Yi, Xiao, Zheng, Tang, Chengyuan, Li, Ying. 2022. Anp32e promotes renal interstitial fibrosis by upregulating the expression of fibrosis-related proteins. In International journal of biological sciences, 18, 5897-5912. doi:10.7150/ijbs.74431. https://pubmed.ncbi.nlm.nih.gov/36263179/

2. Zhu, Xiaowen, Zou, Yumin, Wu, Tong, Wang, Qingdong, Zhang, Meijia. 2022. ANP32E contributes to gastric cancer progression via NUF2 upregulation. In Molecular medicine reports, 26, . doi:10.3892/mmr.2022.12791. https://pubmed.ncbi.nlm.nih.gov/35795988/

3. Sun, Li-Ying, Ke, Shao-Bo, Li, Bo-Xin, Liu, Yi, Chen, Yong-Shun. 2024. ANP32E promotes esophageal cancer progression and paclitaxel resistance via P53/SLC7A11 axis-regulated ferroptosis. In International immunopharmacology, 144, 113436. doi:10.1016/j.intimp.2024.113436. https://pubmed.ncbi.nlm.nih.gov/39566382/

4. Santa-Coloma, Tomás A. . Anp32e (Cpd1) and related protein phosphatase 2 inhibitors. In Cerebellum (London, England), 2, 310-20. doi:. https://pubmed.ncbi.nlm.nih.gov/14964690/