PML Nuclear Body Biogenesis, Carcinogenesis, and Targeted Therapy

Oligomerization mediated by the conserved RBCC motif is essential for PML NB assembly. PML NBs are thought to adopt a phase-separation stage in their biogenesis pathway. PML NBs are important regulators of genome organization. Oligomerization may also be an important factor in leukemogenesis. Oligomerization-driven carcinogenesis is widely observed in solid tumors and other diseases. PML NBs play dual roles as tumor suppressors and oncogenic drivers in various human cancers. PML NBs and oncogenic oligomerization are promising targets in cancer treatment. Targeted therapy has become increasingly important in cancer therapy. For example, targeting the promyelocytic leukemia PML protein in leukemia has proved to be an effective treatment. PML is the core component of super-assembled structures called PML nuclear bodies (NBs). Although this nuclear megaDalton complex was first observed in the 1960s, the mechanism of its assembly remains poorly understood. We review recent breakthroughs in the PML field ranging from a revised assembly mechanism to PML-driven genome organization and carcinogenesis. In addition, we highlight that oncogenic oligomerization might also represent a promising target in the treatment of leukemias and solid tumors. Targeted therapy has become increasingly important in cancer therapy. For example, targeting the promyelocytic leukemia PML protein in leukemia has proved to be an effective treatment. PML is the core component of super-assembled structures called PML nuclear bodies (NBs). Although this nuclear megaDalton complex was first observed in the 1960s, the mechanism of its assembly remains poorly understood. We review recent breakthroughs in the PML field ranging from a revised assembly mechanism to PML-driven genome organization and carcinogenesis. In addition, we highlight that oncogenic oligomerization might also represent a promising target in the treatment of leukemias and solid tumors. extrachromosomal circular telomeric DNA composed of a contiguous C-rich strand and nicked G-rich complementary strand. C-circles are a quantitative biomarker of ALT activity. the genome contains chromatin territories, compartments, and topologically associated domains that are precisely packaged inside the nucleus. This organization plays a crucial role in mediating cellular biological processes including DNA replication, transcription, and cell division. the networking of a variety of biomolecules that work together. This coordination is achieved mostly by diverse protein–protein interactions (including SUMO–SIM-like association) and protein–DNA interactions. oligomerization refers to the process of converting a monomer or a mixture of monomers into an oligomer. In the context of leukemia/solid tumor development, oncogenic fusions derived from chromosomal translocations may enhance intermolecular oligomerization, leading to carcinogenesis. the creation of two distinct phases from a single homogeneous mixture, such as oil and water. Phase separation plays a crucial role in a variety of cellular processes, especially in the formation of membraneless organelles. matrix-associated domains 0.1–2 μm in diameter in most cell lines and many tissues. They are proposed to anchor and regulate many cellular functions. covalent and enzymatic modifications of proteins that take place following protein biosynthesis. PTMs including SUMOylation, phosphorylation, acetylation are catalyzed by a variety of enzymes that recognize specific target sequences in specific proteins. a classic type of PTM. In the process of SUMOylation, a small ubiquitin-related modifier protein (SUMO) is covalently linked to a lysine residue in the target protein through the activities of different ligases (termed E1, E2, and E3). a potent treatment/drug that targets the specific genes, proteins, or tissue environment in cancer development. Targeted therapy is recognized as a potent method to fight cancer, resulting in better overall survival rate and quality of life.