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Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Updated: Jul 18, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

A cytoplasmic PML mutant inhibits p53 function.

Cristian Bellodi1, Karin Kindle, Francesca Bernassola

  • 1MRC Toxicology Unit, Leicester, UK.

Cell Cycle (Georgetown, Tex.)
|December 19, 2006
PubMed
Summary

Cytoplasmic promyelocytic leukaemia (PML) proteins, previously uncharacterized, relocate nuclear PML, disrupt PML nuclear bodies, and inhibit p53 functions, impacting cell survival in aggressive acute promyelocytic leukaemia (APL).

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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Genetics

Background:

  • The promyelocytic leukaemia gene (Pml) acts as a tumor suppressor, notably in acute promyelocytic leukaemia (APL) through its fusion with RAR alpha.
  • While nuclear PML (nPML) is well-studied for its role in PML nuclear bodies (PML-NBs) and p53 regulation, cytoplasmic PML isoforms are less understood.
  • Mutations leading to truncated cytoplasmic PML proteins (Mut PML) are found in aggressive APL cases.

Purpose of the Study:

  • To investigate the role and impact of cytoplasmic PML proteins on nuclear PML functions and cellular regulation.
  • To elucidate the mechanism by which cytoplasmic PML affects PML nuclear bodies and p53 activity.
  • To understand the implications of cytoplasmic PML expression in aggressive APL.

Main Methods:

  • Characterization of cytoplasmic PML protein localization and its effect on PML nuclear bodies.
  • Assessment of p53 transcriptional, growth suppressive, and apoptotic functions in the presence of cytoplasmic PML.
  • Analysis of missense mutations leading to truncated cytoplasmic PML proteins.

Main Results:

  • Cytoplasmic PML induces the relocation of nPML from PML nuclear bodies to the cytoplasm, reducing PML-NB numbers.
  • Mut PML significantly inhibits p53's transcriptional, growth suppressive, and apoptotic activities.
  • Cytoplasmic expression of PML demonstrates a survival advantage through p53 inhibition.

Conclusions:

  • Cytoplasmic PML proteins play a critical role in regulating nuclear PML functions and cellular fate.
  • The aberrant cytoplasmic expression of PML, particularly Mut PML, contributes to oncogenesis by inactivating the tumor suppressor p53.
  • These findings highlight cytoplasmic PML as a potential therapeutic target in APL and other cancers.