Related Experiment Video

Updated: May 24, 2026

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence

Pier Paolo Scaglioni1, Andrea Rabellino, Thomas M Yung

  • 1Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. pier.scaglioni@utsouthwestern.edu

EMBO Molecular Medicine
|February 24, 2012
PubMed

Insights

Oncogenic K-RAS triggers cellular senescence by increasing PML protein, even without p53. This process relies on enhanced PML translation, crucial for tumor suppression and offering new therapeutic avenues for cancers like APL.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Oncogene-induced cellular senescence (OIS) is a tumor suppression mechanism.
  • OIS is often linked to transcriptional changes and the p53 tumor suppressor.
  • PML (Promyelocytic Leukemia) protein is a known OIS mediator and tumor suppressor.

Purpose of the Study:

  • To investigate the role of PML protein upregulation in oncogenic K-RAS-induced OIS.
  • To elucidate the molecular mechanisms driving PML upregulation by oncogenic K-RAS, particularly in a p53-independent manner.
  • To determine the significance of PML mRNA translation in OIS and tumor suppression.

Main Methods:

  • Utilized primary cell cultures expressing oncogenic K-RAS.
  • Analyzed PML protein and mRNA levels under oncogenic stress.
  • Investigated the RAS/MEK1/mTOR/eIF4E signaling pathway.
  • Examined PML mRNA association with polysomes.
  • Assessed the role of the PML 5' untranslated region in translation and OIS.

Main Results:

  • Oncogenic K-RAS induces PML protein upregulation via the RAS/MEK1/mTOR/eIF4E pathway, independent of p53.
  • PML mRNA selectively associates with polysomes, indicating translational control.
  • The 5' untranslated region of PML mRNA is essential for its upregulation and efficient OIS.
  • PML translation upregulation is a key mechanism in K-RAS-driven OIS.

Conclusions:

  • Translational control of PML is a critical mechanism in oncogene-induced cellular senescence.
  • Selective translation initiation of PML plays a significant role in tumor suppression.
  • Targeting PML translation offers potential therapeutic strategies for solid tumors and acute promyelocytic leukemia (APL).

More Related Videos

Techniques to Induce and Quantify Cellular Senescence06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

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 daughter...
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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...