Related Experiment Video

Updated: Jun 22, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

932

Nuclear export of PML promotes p53-mediated apoptosis and ferroptosis

Yue Ni1, Hongce Chen2, Qiuqiang Zhan3

  • 1MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Centre for Optical and Electromagnetic Research, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510631, China.

Cellular Signalling
|June 29, 2024
PubMed

Insights

Promyelocytic leukemia protein (PML) promotes programmed cell death (apoptosis) and iron-dependent cell death (ferroptosis). PML

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Promyelocytic leukemia protein (PML) is a known tumor suppressor.
  • PML influences critical cellular processes including cell cycle, apoptosis, senescence, and metabolism.

Purpose of the Study:

  • To investigate the role of PML in promoting apoptosis and ferroptosis.
  • To elucidate the mechanisms underlying PML-mediated cell death and proliferation inhibition.

Main Methods:

  • Over-expression and knockdown of PML.
  • Assessment of apoptosis markers (nuclear condensation, mitochondrial membrane potential, Bcl-2 family proteins).
  • Measurement of reactive oxygen species (ROS) and lipid ROS.
  • Analysis of ferroptosis markers (Malondialdehyde, SLC7A11, GPX4 expression).
  • Investigation of p53 involvement and PML nuclear export.

Main Results:

  • PML over-expression inhibited cell proliferation and migration.
  • PML enhanced apoptosis by altering mitochondrial potential and regulating Bcl-2 family proteins.
  • PML promoted ferroptosis by increasing lipid ROS and MDA, and downregulating SLC7A11 and GPX4.
  • p53 knockdown partially reversed PML's effects on ferroptosis markers and ROS levels.
  • PML translocation from nucleus to cytoplasm further promoted cell death and inhibited proliferation.

Conclusions:

  • PML significantly promotes both apoptosis and ferroptosis.
  • The tumor suppressor activity of PML involves p53-dependent and independent pathways.
  • Nuclear export of PML is a key event in its function to induce cell death and suppress proliferation.
Keywords:
ApoptosisFerroptosisNuclear exportPMLp53

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

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

Published on: August 4, 2019

9.5K
Assays for the Degradation of Misfolded Proteins in Cells10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

12.0K

Related Concept Videos

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...
4.5K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.4K
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K