Pias2-KO Mouse

PIAS2, also known as protein inhibitor of activated STAT 2, is a key modulator in multiple biological processes. It is involved in signal transduction pathways, particularly those regulated by transcription factors such as NF-κB, IRF3, and JAK/STAT [2]. PIAS2 has SUMO E3 ligase activity which allows it to modify proteins through SUMOylation, influencing various cellular functions [3,5].

In the context of diseases, in sporadic Parkinson disease dementia (sPDD), elevated PIAS2 was associated with defective neuronal IFNβ-IFNAR signaling. Overexpressing PIAS2 in mouse brains caused motor and cognitive impairments, intraneuronal phosphorylated α-synuclein accumulation, and dopaminergic neuron loss. Conversely, PIAS2 knockdown in Ifnb-/- mice rescued the clinicopathological manifestations of PDD by restoring mitochondrial homeostasis and relevant signaling pathways [1]. In anaplastic carcinomas, depletion of the PIAS2β isoform specifically inhibited the growth of cancer cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts in vivo, as PIAS2β is required for proper mitotic spindle and centrosome assembly [4].

In summary, PIAS2 plays a significant role in regulating cellular functions through its involvement in signal transduction and SUMOylation. Research using mouse models has revealed its contribution to neurodegenerative diseases like sPDD and cancer, highlighting its potential as a therapeutic target for these conditions.

References:

1. Magalhaes, Joana, Tresse, Emilie, Ejlerskov, Patrick, Gasser, Thomas, Issazadeh-Navikas, Shohreh. 2021. PIAS2-mediated blockade of IFN-β signaling: a basis for sporadic Parkinson disease dementia. In Molecular psychiatry, 26, 6083-6099. doi:10.1038/s41380-021-01207-w. https://pubmed.ncbi.nlm.nih.gov/34234281/

2. Zu, Shaopo, Xue, Qian, He, Zhuoliang, Jiao, Peirong, Liao, Ming. 2020. Duck PIAS2 negatively regulates RIG-I mediated IFN-β production by interacting with IRF7. In Developmental and comparative immunology, 108, 103664. doi:10.1016/j.dci.2020.103664. https://pubmed.ncbi.nlm.nih.gov/32151676/

3. Zu, Shaopo, Xue, Qian, He, Zhuoliang, Jiao, Peirong, Liao, Ming. 2020. Duck PIAS2 Promotes H5N1 Avian Influenza Virus Replication Through Its SUMO E3 Ligase Activity. In Frontiers in microbiology, 11, 1246. doi:10.3389/fmicb.2020.01246. https://pubmed.ncbi.nlm.nih.gov/32595623/

4. Rodrigues, Joana S, Chenlo, Miguel, Bravo, Susana B, Cameselle-Teijeiro, José Manuel, Alvarez, Clara V. 2024. dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe. In Nature communications, 15, 3736. doi:10.1038/s41467-024-47751-1. https://pubmed.ncbi.nlm.nih.gov/38744818/

5. Du, Junfeng, Du, Yujia, Chen, Lang, Liu, Hongwei. 2023. IL-17 promotes melanoma through TRAF2 as a scaffold protein recruiting PIAS2 and ELAVL1 to induce EPHA5. In Biochimica et biophysica acta. Molecular cell research, 1870, 119547. doi:10.1016/j.bbamcr.2023.119547. https://pubmed.ncbi.nlm.nih.gov/37481078/