Related Experiment Video

Updated: Jul 24, 2026

Gene-targeted Random Mutagenesis to Select Heterochromatin-destabilizing Proteasome Mutants in Fission Yeast
07:18

Gene-targeted Random Mutagenesis to Select Heterochromatin-destabilizing Proteasome Mutants in Fission Yeast

Published on: May 15, 2018

A "no-hybrids" screen for functional antagonizers of human p53 transactivator function: dominant negativity in

S Waddell1, J R Jenkins, T Proikas-Cezanne

  • 1Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Oncogene
|October 11, 2001
PubMed

Insights

Researchers created a novel yeast screen to find human p53 protein modulators. This "no-hybrids" system identifies compounds that affect p53 activity, crucial for cancer research.

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • Cancer Biology

Background:

  • The tumor suppressor protein p53 plays a critical role in preventing cancer.
  • Developing methods to identify modulators of p53 activity is essential for therapeutic development.

Purpose of the Study:

  • To establish a functional screening system in Schizosaccharomyces pombe to identify antagonizers and modulators of human p53 activity.
  • To validate the utility of the developed screening system for various p53-related interactions and homologues.

Main Methods:

  • Development of a "no-hybrids" screen in fission yeast based on the transactivator activity of human p53.
  • Conditional lethality of functional full-length human p53 drives the screen; co-expression of inhibitors promotes survival.
  • Validation using interactions with SV40 large T antigen, Mdm2, p53 mutants, and screening for dominant-negative p53 fragments.

Main Results:

  • Successful establishment and validation of the "no-hybrids" screen in Schizosaccharomyces pombe.
  • Demonstrated ability to model known p53 interactions and identify novel modulators.
  • Confirmed the system's capacity to detect evolutionarily distant p53 homologues based on transactivator function.

Conclusions:

  • The "no-hybrids" screen provides a powerful tool for discovering modulators of p53 function.
  • This system is applicable for identifying cellular and viral factors impacting p53 activity.
  • The screen holds significant potential for advancing cancer research and therapeutic strategies targeting p53.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe07:55

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe

Published on: March 7, 2019

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.
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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...
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...