Related Experiment Video
Updated: Jul 14, 2026

14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Genetic analysis of p53 nuclear importation.
1Department of Cell Biology and Anatomy, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Oncogene
|June 30, 2007
Summary
Researchers investigated how the p53 tumor suppressor protein enters the nucleus. They discovered a specific pathway for p53 nuclear import, involving both soluble and insoluble cellular components.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The p53 tumor suppressor protein plays a critical role in preventing cancer.
- Nuclear transport is essential for p53 activation, but its regulation remains unclear.
- Understanding p53 subcellular localization is crucial for cancer therapy.
Purpose of the Study:
- To investigate the mechanisms regulating the nuclear import of p53.
- To identify factors involved in p53 nuclear translocation.
- To explore the existence of a specific import pathway for p53.
Main Methods:
- Utilized mutant cell lines resistant to temperature-sensitive murine p53 (tsp53).
- Employed a digitonin-permeabilized cell in vitro nuclear import system.
- Performed complementation assays with soluble and insoluble cellular fractions.
Main Results:
- p53 was found to be predominantly cytoplasmic in most tested mutant cell lines.
- Cytosols from these cell lines failed to support nuclear import of p53 substrates but supported import of other NLS-containing proteins.
- Both soluble and insoluble protein components were identified as necessary for p53 nuclear import.
Conclusions:
- A p53 nuclear localization signal (NLS)-selective nuclear import pathway exists.
- This pathway involves the coordinated function of both soluble and insoluble cellular proteins.
- Further research into this pathway could reveal new therapeutic targets for cancer.
Related Concept Videos
Nuclear Localization Signals and Import
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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...
Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
Export of Mitochondrial and Chloroplast Genes
A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred irrespective...

