Post-translational modifications of PML: consequences and implications

Abstract

The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies. Emerging evidences indicated that PML actively participates in many aspects of cellular processes, but the molecular mechanisms underlying PML regulation in response to stress and environmental cues are not complete. Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML. In this review, we discuss the fast-moving horizon of post-translational modifications targeting PML.

The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for SUMOylation of the Major Immediate Early Protein IE1 of Human Cytomegalovirus

“…ND10, which are defined by the presence of the three major ND10 factors PML, hDaxx, and Sp100, are implicated in the coordinated regulation of diverse cellular processes, like DNA damage repair, apoptosis, and senescence (reviewed in reference 14). Interestingly, recent studies support the hypothesis that ND10 may also provide a nuclear platform for posttranslational modifications, like phosphorylation, acetylation, and SUMOylation (15)(16)(17). The last has been suggested by Van Damme and colleagues, who set up a manually curated network of the PML-NB interactome.…”

“…Evidence is growing that ND10 can be regarded as subnuclear sites that provide a platform for the regulation of multiple PTM by hosting components of various PTM pathways (15)(16)(17). The idea of ND10 as a nuclear hot spot for PTM might explain how PML and PML-NBs are able to participate in such a plethora of diverse cellular processes.…”

Ablation of Promyelocytic Leukemia Protein (PML) Re-patterns Energy Balance and Protects Mice from Obesity Induced by a Western Diet

“…unclear. PML is primarily enriched in the PML NBs, which are thought to be a nuclear depot that contains transient or permanent residents (34). More than 160 proteins have been shown to interact with PML (35).…”

“…More than 160 proteins have been shown to interact with PML (35). It is believed that there is a marked change in NB protein composition in response to extracellular stimuli, including DNA damage agents, viral infection, and growth factors (34,36). By altering the components in the PML NBs, proteins involved in cellular processes such as transcriptional regulation, translation control, cell cycle progression, anti-viral response, DNA damage response and repair, and apoptosis are transiently brought into close proximity of, or dissociate from each other, thus promoting a timely and efficient response through protein-protein interactions and protein modifications.…”

PML nuclear bodies: Assembly and oxidative stress-sensitive sumoylation

“…26,41 PML can also be subjected to multiple post-translational modifications, particularly phosphorylation and acetylation, which might further regulate NB biogenesis and partner recruitment. [63][64][65] In response to DNA damaging stress, multiple serine residues on PML are phosphorylated. The latter was proposed to facilitate DNA damage-induced apoptosis.…”