PML Nuclear bodies: the cancer connection and beyond

Nucleus. 2024 Dec;15(1):2321265. doi: 10.1080/19491034.2024.2321265. Epub 2024 Feb 27.

Abstract

Promyelocytic leukemia (PML) nuclear bodies, membrane-less organelles in the nucleus, play a crucial role in cellular homeostasis. These dynamic structures result from the assembly of scaffolding PML proteins and various partners. Recent crystal structure analyses revealed essential self-interacting domains, while liquid-liquid phase separation contributes to their formation. PML bodies orchestrate post-translational modifications, particularly stress-induced SUMOylation, impacting target protein functions. Serving as hubs in multiple signaling pathways, they influence cellular processes like senescence. Dysregulation of PML expression contributes to diseases, including cancer, highlighting their significance. Therapeutically, PML bodies are promising targets, exemplified by successful acute promyelocytic leukemia treatment with arsenic trioxide and retinoic acid restoring PML bodies. Understanding their functions illuminates both normal and pathological cellular physiology, guiding potential therapies. This review explores recent advancements in PML body biogenesis, biochemical activity, and their evolving biological roles.

Keywords: Nuclear bodies; PML; SUMO; oxidative stress; post-translational modifications; senescence; transcription.

Publication types

  • Review

MeSH terms

  • Humans
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Leukemia, Promyelocytic, Acute* / metabolism
  • Leukemia, Promyelocytic, Acute* / pathology
  • Nuclear Proteins / metabolism
  • Promyelocytic Leukemia Nuclear Bodies*
  • Promyelocytic Leukemia Protein / genetics
  • Promyelocytic Leukemia Protein / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism

Substances

  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors

Grants and funding

This work was supported by the Collège de France, INSERM, CNRS, Université de Paris, Labex Memolife (VLB), ITMO Cancer PCSI (C22028DS, VLB), Fondation du Collège de France, European Research Council Advanced Grant 785917–PML-THERAPY (to H.d.T.).Majdouline Abou-Ghali is supported by ITMO cancer PCSI under Grant C22028DS, VLB.