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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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PML nuclear bodies: regulation, function and therapeutic perspectives.

Umut Sahin1, Valérie Lallemand-Breitenbach, Hugues de Thé

  • 1Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis, Paris, France; INSERM UMR 944, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France; CNRS UMR 7212, Hôpital St. Louis, Paris, France.

The Journal of Pathology
|August 21, 2014
PubMed
Summary

Promyelocytic leukemia nuclear bodies (NBs) are cellular factories responding to stress and interferon. These structures play roles in viral restriction, metabolism, and senescence, offering potential therapeutic targets for diseases like cancer and neurodegeneration.

Keywords:
PMLRNF4arsenicinterferonoxidative stressp53senescence

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Promyelocytic leukemia nuclear bodies (PML NBs) were initially identified via electron microscopy.
  • PML NBs were later rediscovered through their reversible disruption in a specific leukemia.
  • These nuclear bodies are dynamic structures involved in various cellular processes.

Purpose of the Study:

  • To elucidate the multifaceted roles of PML nuclear bodies in cellular responses.
  • To explore the connection between PML NBs, sumoylation, and cellular stress.
  • To investigate the potential therapeutic applications of PML NBs in disease.

Main Methods:

  • Electron microscopy for initial identification.
  • Observation of treatment-reversible disruption in leukemia models.
  • Analysis of protein recruitment and functional assays related to interferon and oxidative stress responses.

Main Results:

  • PML NBs function as sumoylation factories, responding to interferon and oxidative stress.
  • They are implicated in viral restriction, enhanced proteolysis, metabolic regulation, and senescence.
  • PML NBs serve as crucial markers of cellular stress.

Conclusions:

  • PML NBs are critical regulators of cellular stress responses and innate immunity.
  • Their diverse functions highlight their importance in maintaining cellular homeostasis.
  • PML NBs represent promising pharmacological targets for treating cancer, viral infections, and neurodegenerative diseases.