Pml, short for promyelocytic leukemia protein, is a key organizer of PML nuclear bodies (NBs), membrane-less organelles in the nucleus. It belongs to the tripartite motif (TRIM) family. PML NBs play a crucial role in cellular homeostasis, influencing multiple signaling pathways such as those related to senescence, apoptosis, cell cycle, and DNA damage responses [1,2,3,5]. Dysregulation of Pml is associated with diseases, especially cancer [1].

One of the key findings is in acute promyelocytic leukemia (APL), where the oncoprotein PML/RARα inhibits PML NBs assembly, leading to leukemogenesis [3]. Also, murine PML-null primary cells are resistant to TGF-β-induced apoptosis, indicating Pml's role in this process [4]. Pml isoforms generated by alternative splicing have distinct functions; for example, cytoplasmic Pml activates TGF-β signaling, while nuclear Pml is involved in TGF-β-induced caspase 8 activation and apoptosis [4].

In conclusion, Pml is essential for maintaining cellular homeostasis through its role in PML NBs. Its dysregulation is closely related to cancer, especially APL. Studies on Pml-null mouse models have revealed its role in TGF-β-induced apoptosis, highlighting its importance in understanding disease mechanisms and potentially developing targeted therapies [3,4].

References:

1. Abou-Ghali, Majdouline, Lallemand-Breitenbach, Valérie. 2024. PML Nuclear bodies: the cancer connection and beyond. In Nucleus (Austin, Tex.), 15, 2321265. doi:10.1080/19491034.2024.2321265. https://pubmed.ncbi.nlm.nih.gov/38411156/

2. Silonov, Sergey A, Smirnov, Eugene Y, Kuznetsova, Irina M, Turoverov, Konstantin K, Fonin, Alexander V. 2023. PML Body Biogenesis: A Delicate Balance of Interactions. In International journal of molecular sciences, 24, . doi:10.3390/ijms242316702. https://pubmed.ncbi.nlm.nih.gov/38069029/

3. Li, Yuwen, Ma, Xiaodan, Meng, Guoyu. 2020. PML nuclear body biogenesis and oligomerization-driven leukemogenesis. In Blood science (Baltimore, Md.), 2, 7-10. doi:10.1097/BS9.0000000000000034. https://pubmed.ncbi.nlm.nih.gov/35399865/

4. El-Asmi, Faten, Chelbi-Alix, Mounira K. 2020. [PML isoforms and TGF-β response]. In Medecine sciences : M/S, 36, 50-56. doi:10.1051/medsci/2019269. https://pubmed.ncbi.nlm.nih.gov/32014098/

5. Hsu, Kuo-Sheng, Kao, Hung-Ying. 2018. PML: Regulation and multifaceted function beyond tumor suppression. In Cell & bioscience, 8, 5. doi:10.1186/s13578-018-0204-8. https://pubmed.ncbi.nlm.nih.gov/29416846/