Related Experiment Video

Updated: Feb 19, 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

8.6K

SOCS1 regulates senescence and ferroptosis by modulating the expression of p53 target genes

Emmanuelle Saint-Germain1, Lian Mignacca1, Mathieu Vernier2

  • 1Département de Biochimie et Médecine Moléculaire; Université de Montréal, Montréal, Québec H3C 3J7, Canada.

Aging
|October 31, 2017
PubMed

Insights

Suppressor of Cytokine Signaling 1 (SOCS1) activates p53 and promotes senescence. SOCS1 targets genes involved in ferroptosis, influencing cell death susceptibility based on senescence triggers.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Senescence

Background:

  • The tumor-suppressive role of p53 is complex and not fully elucidated.
  • Aberrant Janus Kinase/Signal Transducer and Activator of Transcription 5 (JAK/STAT5) pathway activation is linked to tumorigenesis.
  • Suppressor of Cytokine Signaling 1 (SOCS1) is crucial for p53 activation and cellular senescence in this context.

Purpose of the Study:

  • To identify p53 target genes involved in senescence induced by oncogenic STAT5A.
  • To investigate the role of SOCS1 in regulating these p53 target genes and cellular ferroptosis susceptibility.

Main Methods:

  • Transcriptome characterization of STAT5A-expressing cells following SOCS1 inhibition.
  • Analysis of p53 target gene expression, including secreted proteins and metabolic regulators.
  • Assessment of cellular ferroptosis sensitivity upon SOCS1 modulation and induction by oncogenic factors (STAT5A, RasV12, PML).

Main Results:

  • SOCS1 inhibition revealed a set of SOCS1-dependent p53 target genes, including those regulating oxidative metabolism and ferroptosis.
  • Exogenous SOCS1 induced p53 target genes and sensitized cells to ferroptosis by reducing cystine transporter SLC7A11 and glutathione levels.
  • While SOCS1, STAT5A, RasV12, and PML all induced SOCS1 and p53 target genes during senescence, only SOCS1 sensitized cells to ferroptosis, whereas PML conferred resistance.

Conclusions:

  • Cellular senescence exhibits varying susceptibility to ferroptosis depending on the inducing oncogenic trigger.
  • SOCS1 plays a key role in regulating p53 target genes and modulating ferroptosis sensitivity during senescence.
  • Targeting ferroptosis resistance pathways could offer a strategy for eliminating senescent cancer cells.
Keywords:
KAP1ferroptosissenescencesuppressor of cytokine signalingtumor suppressor

More Related Videos

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics04:01

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

Published on: March 15, 2024

2.0K

Related Concept Videos

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...
4.5K
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...
5.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K
Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
540
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

4.0K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.6K