Related Experiment Video

Updated: May 2, 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

8.9K

Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence

Hui-Kuan Lin1, Zhenbang Chen, Guocan Wang

  • 1Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.

Nature
|March 19, 2010
PubMed

Insights

Skp2 E3-ubiquitin ligase inactivation triggers potent tumor-suppressive senescence independent of the p19(Arf)-p53 pathway. This suggests Skp2 inhibition as a potential cancer prevention and therapy strategy.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Cellular senescence opposes tumor initiation and promotion.
  • Senescence is often linked to the p19(Arf)-p53 pathway.
  • Skp2 E3-ubiquitin ligase acts as a proto-oncogene, frequently overexpressed in cancers.

Purpose of the Study:

  • To investigate the role of Skp2 in senescence induction.
  • To explore Skp2-independent senescence pathways.
  • To evaluate Skp2 inhibition as a cancer therapeutic strategy.

Main Methods:

  • Genetic inactivation of Skp2 in mice and cells.
  • Induction of oncogenic stress and tumor suppressor gene inactivation.
  • Analysis of senescence markers and signaling pathways (p19(Arf)-p53, Atf4, p27, p21).
  • Treatment with a Skp2-SCF complex inhibitor.

Main Results:

  • Skp2 inactivation alone does not induce senescence, but potentiates senescence under oncogenic stress or tumor suppressor loss.
  • Skp2-dependent senescence bypasses the p19(Arf)-p53 pathway and DNA damage, relying on Atf4, p27, and p21.
  • Genetic Skp2 inactivation induces senescence even when p19(Arf)-p53 is impaired.
  • Skp2 inhibition triggers senescence and tumor regression in preclinical models.

Conclusions:

  • Skp2 plays a critical role in regulating senescence, particularly under oncogenic stress.
  • Targeting Skp2 offers a novel therapeutic avenue for cancer.
  • Pharmacological inhibition of Skp2 shows promise for cancer prevention and treatment.

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

5.7K
Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

371

Related Concept Videos

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.
32.1K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
8.5K
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...
4.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.3K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
2.4K