PML : PML nuclear body scaffold
Description
The PML (PML nuclear body scaffold) is a protein-coding gene located on chromosome 15.
The PML gene provides instructions for a protein that acts as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The PML protein is found in distinct structures in the nucleus of a cell called PML nuclear bodies (PML-NBs). In the PML-NBs, the PML protein interacts with other proteins that are involved in cell growth and division (proliferation) and self-destruction (apoptosis). The PML protein is able to block cell proliferation and induce apoptosis in combination with other proteins. Researchers believe that the structure of the PML-NBs is required for blocking proliferation and inducing apoptosis.
The PML protein, encoded by the PML gene, plays a crucial role in various cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. It primarily functions within PML-nuclear bodies (PML-NBs), acting as a scaffold that allows other proteins to move in and out. This process is regulated by SUMO-mediated modifications and interactions. PML inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E's affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs. Isoform PML-4, specifically, has a complex role in regulating apoptosis and growth suppression. It activates RB1 and inhibits AKT1 through interactions with PP1 and PP2A phosphatases, respectively. It also negatively impacts the PI3K pathway by inhibiting MTOR and activating PTEN, while positively regulating p53/TP53 by promoting its acetylation and phosphorylation and inhibiting its MDM2-dependent degradation. Additional functions of isoform PML-4 include acting as a transcriptional repressor of TBX2 during cellular senescence, regulating double-strand break repair in gamma-irradiation-induced DNA damage responses, acting as a negative regulator of telomerase, and regulating PER2 nuclear localization and circadian function. Isoform PML-6 inhibits the activity of the tetrameric form of PKM. Nuclear isoforms (PML-1, PML-2, PML-3, PML-4, and PML-5) work together with SATB1 to remodel chromatin loops locally and regulate gene expression at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma-induced MHC II gene transcription through regulating CIITA. Cytoplasmic PML regulates the TGF-beta signaling pathway. PML also regulates the transcriptional activity of ELF4 and acts as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.
PML is also known as MYL, PP8675, RNF71, TRIM19.
