Functions and dys-functions of promyelocytic leukemia protein PML

  • Maurizio Previati
  • Sonia Missiroli
  • Mariasole Perrone
  • Natascia Caroccia
  • Federico Paliotto
  • Daniela Milani
  • Carlotta Giorgi
Current topics in Biology
  • 12 Downloads

Abstract

The promyelocytic leukemia protein PML has been previously recognized as a critical and essential regulator of a broad number of cellular functions. At nuclear level PML forms the PML-nuclear bodies, where it can sequester and influence the post-translational modification of a wide number of proteins, ultimately affecting their regulative role in DNA transcription. In such a way, PML acts as a key player in strategic cellular activities like as the antiviral defense, in the regulation of the cell cycle, in senescence and programmed cell death. In addition, PML can redistribute also at cytoplasmic level, where it associates to the endoplasmic reticulum or is recruited to mitochondrial-associated membranes. Here it can interact with key cellular proteins like as p53 and influence cell metabolism, mitochondrial calcium upload and autophagy. Altogether, all these findings depict PML as a protein able to exert a widespread action mainly focused on pro-apoptotic and cytostatic activities. Anyway, presence of “Janus-like” pro-tumoral behaviors have been reported, prompting for further investigation to better dissect and highlight all the possible roles that PML can assume in the different physiological or pathological environments. In this review, we discuss the role of PML in multiple cellular functions and pathologic scenarios and summarize the players that control PML protein both at nuclear and at cytoplasmic level.

Keywords

PML functions Antiviral response Senescence Cell death Metabolism Cancer 

Notes

Acknowledgements

Fundings were provided by local funds from the University of Ferrara, the Italian Association for Cancer Research (AIRC: IG-19803), the Italian Ministry of Health, and by a Fondazione Cariplo grant.

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Copyright information

© Accademia Nazionale dei Lincei 2018

Authors and Affiliations

  1. 1.Section of Human Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, School of Medicine, and Laboratory for Technologies of Advanced Therapies (LTTA)University of FerraraFerraraItaly
  2. 2.Section of Pathology, Oncology and Experimental Biology, Department of Morphology, Surgery and Experimental Medicine, School of Medicine, and Laboratory for Technologies of Advanced Therapies (LTTA)University of FerraraFerraraItaly

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