Subnuclear localization of proteins encoded by the oncogene v-myb and its cellular homolog c-myb

Insights

The viral Myb protein (p45v-myb) and chicken Myb protein (p75c-myb) associate with both chromatin and the nuclear matrix. This suggests Myb proteins interact with multiple nuclear targets for their function.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • The retroviral transforming gene v-myb encodes a nuclear protein (p45v-myb), a modified version of the chicken c-myb gene product (p75c-myb).
  • Both p45v-myb and p75c-myb are nuclear proteins, suggesting a role in nuclear functions.

Purpose of the Study:

  • To determine the subnuclear locations of p45v-myb and p75c-myb.
  • To identify potential nuclear targets involved in v-myb-mediated cellular transformation and c-myb function.

Main Methods:

  • Nuclear extraction using varying salt concentrations.
  • Assessment of DNA-binding activity.
  • Nuclease digestion and analysis of protein association with nuclear substructures.

Main Results:

  • 80-90% of both p45v-myb and p75c-myb were released from nuclei at low salt concentrations and showed DNA-binding activity.
  • A minor fraction (10-20%) of both proteins remained tightly associated with nuclei even at high salt concentrations (2 M NaCl).
  • These proteins appear to associate with both chromatin and the nuclear matrix.

Conclusions:

  • Both viral and cellular Myb proteins are associated with chromatin and the nuclear matrix.
  • Myb protein function likely involves interactions with multiple nuclear targets, including chromatin and the nuclear matrix.

Related Concept Videos

Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
Nuclear Protein Sorting01:34

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...
Nuclear Localization Signals and Import01:46

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...
Regulation of Nuclear Protein Sorting01:45

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 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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...