PML Nuclear bodies: the cancer connection and beyond

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
• oxidative stress
• PML
• post-translational modifications
• senescence
• SUMO
• transcription

Acknowledgments

We thank Hugues de Thé for intellectual guidance. We thank Caroline Berthier, Omar Ferhi, and Pierre Bercier for critically reading this review.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors contributions

Majdouline Abou-Ghali wrote the manuscript and Valérie Lallemand-Breitenbach supervised and reviewed the manuscript.

Data availability statement

Data sharing is not applicable to this article, as no new data were created or analyzed in this study.

Additional information

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.