PML is essential for multiple apoptotic pathways

Related Experiment Video

Updated: Oct 27, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Z G Wang1, D Ruggero, S Ronchetti

  • 1Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA.

Nature Genetics
|November 7, 1998
PubMed

Insights

The PML gene is crucial for programmed cell death (apoptosis) and tumor suppression. Its absence protects mice from radiation and Fas antibody, highlighting its role in apoptosis and cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • The PML gene acts as a cell growth and tumor suppressor, but its precise mechanisms are unclear.
  • Understanding PML's role in apoptosis is key to deciphering its tumor-suppressive functions.

Purpose of the Study:

  • To elucidate the mechanisms by which PML suppresses tumorigenesis.
  • To investigate PML's role in mediating apoptosis induced by various stimuli.

Main Methods:

  • Utilized Pml-/- mice and cells to assess apoptosis induction.
  • Examined caspase activation pathways in response to DNA damage, Fas, TNF, ceramide, and interferons.

Main Results:

  • Pml is essential for Fas- and caspase-dependent apoptosis induced by DNA damage.
  • Pml deficiency confers resistance to ionizing radiation and anti-Fas antibody.
  • PML-RAR alpha fusion protein in APL inhibits apoptosis by blocking caspase 3 activation.

Conclusions:

  • PML acts as a critical mediator for multiple apoptotic signaling pathways.
  • Inhibition of PML-mediated apoptosis is implicated in the pathogenesis of acute promyelocytic leukemia (APL).

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Detection and Isolation of Apoptotic Bodies to High Purity12:17

Detection and Isolation of Apoptotic Bodies to High Purity

Published on: August 12, 2018

Related Concept Videos

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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.