Related Experiment Video

Updated: Jun 25, 2026

Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter
07:42

Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter

Published on: September 17, 2016

A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53

Jasper Mullenders1, Armida W M Fabius, Mandy Madiredjo

  • 1Division of Molecular Carcinogenesis, Centre for Biomedical Genetics and Cancer Genomics Centre, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Plos One
|March 12, 2009
PubMed
Abstract

Insights

Researchers identified three new genes regulating the p53 pathway, including ARNTL (BMAL1), a circadian clock component. This discovery strengthens the link between circadian rhythm and cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53 tumor suppressor gene is frequently mutated or inactivated in human cancers.
  • Understanding mechanisms of p53 pathway inactivation is crucial for cancer therapy.
  • Identifying novel regulators of p53 function can reveal new therapeutic targets.

Purpose of the Study:

  • To identify novel genes that regulate the p53 tumor suppressor pathway.
  • To investigate the role of these newly identified genes in cancer.

Main Methods:

  • A large-scale RNA interference (RNAi)-based genetic screen using an shRNA library targeting 8,000 human genes.
  • Utilized the shRNA barcode technique for efficient identification of active shRNA vectors.
  • Functional validation of identified genes in cancer cells.

Main Results:

  • Identified three previously unknown regulators of p53 function: ARNTL, RBCK1, and TNIP1.
  • ARNTL (also known as BMAL1) is a core component of the circadian regulatory network.
  • Suppression of ARNTL impairs p53-mediated cell cycle arrest and p21 activation.

Conclusions:

  • Discovered three novel regulators of the p53 pathway.
  • The identification of ARNTL highlights a significant connection between circadian rhythm and cancer.
  • Findings provide new insights into p53 pathway regulation and its role in cancer development.

More Related Videos

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells11:56

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

Published on: September 28, 2017

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
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.
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...
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...
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...