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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...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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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.
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.
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Such genes that act...

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Related Experiment Video

Updated: Jun 5, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
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TSPYL5 suppresses p53 levels and function by physical interaction with USP7.

Mirjam T Epping1, Lars A T Meijer, Oscar Krijgsman

  • 1Division of Molecular Carcinogenesis, Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Nature Cell Biology
|December 21, 2010
PubMed
Summary

High expression of TSPYL5, a gene linked to breast cancer, predicts poor outcomes. TSPYL5 suppresses the tumor suppressor p53 by interacting with USP7, promoting cancer development.

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Published on: August 4, 2019

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • A previously identified gene expression signature predicts poor clinical outcomes in breast cancer.
  • TSPYL5 (TSPY-like 5) is a gene of unknown function within a frequently amplified region on chromosome 8q22 in breast cancer.
  • Amplification of this region suggests a potential role for TSPYL5 in breast oncogenesis.

Purpose of the Study:

  • To investigate the role of TSPYL5 in breast cancer.
  • To determine if TSPYL5 expression is a prognostic marker.
  • To elucidate the molecular mechanism by which TSPYL5 influences breast cancer progression.

Main Methods:

  • Gene expression analysis to correlate TSPYL5 levels with clinical outcome.
  • Mass spectrometry to identify TSPYL5 interacting proteins.
  • Biochemical assays to assess TSPYL5's effect on p53 ubiquitylation and activity.
  • Cell-based assays to evaluate TSPYL5's impact on proliferation, senescence, and transformation.

Main Results:

  • High TSPYL5 expression is an independent marker of poor prognosis in breast cancer.
  • TSPYL5 interacts with ubiquitin-specific protease 7 (USP7).
  • TSPYL5 reduces USP7's deubiquitylase activity towards the p53 tumor suppressor, leading to increased p53 ubiquitylation and degradation.
  • TSPYL5 inhibits p53-target gene activation, overrides p53-dependent cell cycle arrest and senescence, and promotes oncogenic transformation.

Conclusions:

  • TSPYL5 acts as a suppressor of p53 function through its interaction with USP7.
  • TSPYL5 contributes to breast cancer progression by inactivating the p53 tumor suppressor pathway.
  • Targeting the TSPYL5-USP7 interaction may offer a therapeutic strategy for breast cancer.