PARP14, also known as ARTD8 or BAL2, is a poly (ADP-ribose) polymerase. It is a mono-ADP-ribosyl transferase involved in immunity, transcription, and DNA replication stress management [2]. PARP14 utilizes nicotinamide adenine dinucleotide (NAD+) as a substrate to perform mono-ADP-ribosylation modification on target proteins, participating in immune-related cellular responses and signaling pathways [2].

Genetic knockdown of PARP14 in photothrombotic stroke (PT) mice aggravated functional impairment, increased infarct volume, and enhanced post-stroke microglial activation [1]. In contrast, overexpression of PARP14 had the opposite effects, suggesting it restricts microglial activation and promotes functional recovery after stroke [1]. In preclinical cancer models, pharmacological inhibition or knockdown of PARP14 enhanced effector T cell infiltration and decreased regulatory T cells in tumors pre-treated with IFNγ, restoring sensitivity to PD-1 immune checkpoint inhibitor treatment [3]. In acute myeloid leukemia (AML), knockdown of PARP14 inhibited cell proliferation and glycolysis and promoted apoptosis, while overexpression had the opposite effects [4]. In addition, macrophages from PARP14 knockout mice showed limited ability to differentiate into M2-like tumor-associated macrophages (TAMs), and PARP14 inhibitors weakened TAM polarization [5].

In summary, PARP14 plays a crucial role in multiple biological processes and disease conditions. Model-based research, especially gene knockout studies, has revealed its significance in stroke recovery, cancer immunotherapy, AML development, and TAM differentiation, providing potential therapeutic targets for these diseases.

References:

1. Tang, Ying, Liu, Jinchang, Wang, Yu, Xu, Yungen, Yao, Honghong. 2020. PARP14 inhibits microglial activation via LPAR5 to promote post-stroke functional recovery. In Autophagy, 17, 2905-2922. doi:10.1080/15548627.2020.1847799. https://pubmed.ncbi.nlm.nih.gov/33317392/

2. Qin, Wei, Wu, Hong-Jie, Cao, Lu-Qi, Jin, Xi, Cao, Hui-Ling. 2019. Research Progress on PARP14 as a Drug Target. In Frontiers in pharmacology, 10, 172. doi:10.3389/fphar.2019.00172. https://pubmed.ncbi.nlm.nih.gov/30890936/

3. Wong, Chun Wai, Evangelou, Christos, Sefton, Kieran N, Niepel, Mario, Hurlstone, Adam F L. 2023. PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models. In Nature communications, 14, 5983. doi:10.1038/s41467-023-41737-1. https://pubmed.ncbi.nlm.nih.gov/37752135/

4. Zhu, Ying, Liu, Zhirui, Wan, Yiqi, Lu, Chen, Qiu, Fang. 2022. PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression. In Clinical immunology (Orlando, Fla.), 242, 109094. doi:10.1016/j.clim.2022.109094. https://pubmed.ncbi.nlm.nih.gov/35944879/

5. Sturniolo, Isotta, Váróczy, Csongor, Regdon, Zsolt, Schüler, Herwig, Virág, László. 2024. PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype. In International journal of molecular sciences, 25, . doi:10.3390/ijms25073601. https://pubmed.ncbi.nlm.nih.gov/38612413/