Nap1l4, or nucleosome assembly protein 1-like 4, is involved in multiple biological processes. It plays a role in modulating p53 acetylation, which is crucial for regulating cell fate, determining whether cells undergo growth arrest or apoptosis [2]. It also interacts with viral proteins, influencing viral replication. For instance, it has been linked to the replication of porcine circovirus type 2 (PCV2) and Chikungunya virus (CHIKV), highlighting its importance in host-virus interactions [1,3]. Additionally, in pulmonary hypertension, it is related to the regulation of pulmonary artery smooth muscle cell proliferation through a circRNA-mediated mechanism [4].

In terms of disease-related findings, knockout of Nap1l4 in PK15 cells led to an up-regulation of PCV2 Cap and Rep mRNA and protein levels, as well as an increase in PCV2 genomic DNA copies and virus titers, suggesting that Nap1l4 inhibits PCV2 replication through regulating IFN-β production [1]. In melanoma cells, knockdown of Nap1l4 reduced cell migration and invasion, up-regulated p21, down-regulated Slug, decreased the active levels of MMP-2, inhibited apoptosis in DNA-damage-induced conditions, arrested the cell cycle at the G1/S phase, and inhibited cell proliferation, indicating its potential as a therapeutic target for melanoma [5].

In conclusion, Nap1l4 is significant in modulating cell fate, host-virus interactions, and cell proliferation in specific disease contexts. The gene knockout/knockdown models have revealed its role in inhibiting PCV2 replication and potentially controlling melanoma cell proliferation and invasion, providing insights into disease mechanisms and potential therapeutic strategies.

References:

1. Wang, Shengnan, Ren, Xuqian, Li, Jiarong, Zhou, Jiyong, Gu, Jinyan. 2020. NAP1L4 inhibits porcine circovirus type 2 replication via IFN-β signaling pathway. In Veterinary microbiology, 246, 108692. doi:10.1016/j.vetmic.2020.108692. https://pubmed.ncbi.nlm.nih.gov/32605741/

2. Tanaka, Toshiaki, Hozumi, Yasukazu, Martelli, Alberto M, Iino, Mitsuyoshi, Goto, Kaoru. 2019. Nucleosome assembly proteins NAP1L1 and NAP1L4 modulate p53 acetylation to regulate cell fate. In Biochimica et biophysica acta. Molecular cell research, 1866, 118560. doi:10.1016/j.bbamcr.2019.118560. https://pubmed.ncbi.nlm.nih.gov/31634504/

3. Dominguez, Francisco, Shiliaev, Nikita, Lukash, Tetyana, Frolova, Elena I, Frolov, Ilya. 2021. NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation. In Journal of virology, 95, e0083621. doi:10.1128/JVI.00836-21. https://pubmed.ncbi.nlm.nih.gov/34076483/

4. Wang, Xiaoying, Guan, Xiaoyu, Zhu, Xiangrui, Wu, Bingxiang, Zhu, Daling. . CircNAP1L4 regulates pulmonary artery smooth muscle cell proliferation via the NAP1L4-mediated super-enhancer-driven glycolysis gene hexokinase II (HK II) in pulmonary hypertension. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23868. doi:10.1096/fj.202400585RRR. https://pubmed.ncbi.nlm.nih.gov/39102213/

5. Mizuhashi, Satoru, Fukushima, Satoshi, Ishibashi, Takayuki, Kita, Kanako, Ihn, Hironobu. 2021. Nucleosome assembly protein 1-like 4, a new therapeutic target for proliferation and invasion of melanoma cells. In Journal of dermatological science, 102, 16-24. doi:10.1016/j.jdermsci.2021.02.001. https://pubmed.ncbi.nlm.nih.gov/33583643/