The nuclear DEK interactome supports multi-functionality

Eric A Smith1, Eric F Krumpelbeck1, Anil G Jegga2

  • 1Department of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45219.

Proteins
|October 31, 2017
PubMed

Insights

Researchers identified new DEK oncoprotein interactions, revealing its roles in nucleotide synthesis and ribosome formation. This study enhances understanding of DEK

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • DEK oncoprotein is overexpressed in various cancers.
  • Known DEK functions involve chromatin structure, epigenetics, and transcription.
  • Previous studies focused on DEK's DNA-binding and chromatin processing.

Purpose of the Study:

  • To develop the first DEK interactome model.
  • To identify novel DEK binding partners and functions in underexplored areas.
  • To generate mechanism-driven hypotheses for DEK activities.

Main Methods:

  • Utilized tandem-affinity purification coupled with mass spectrometry.
  • Investigated protein-protein interactions of the DEK oncoprotein.

Main Results:

  • Identified IMPDH2, DDX21, and RPL7a as novel DEK binding partners.
  • Discovered a hydroxyurea-specific interaction between DEK and replication protein A (RPA).
  • These findings suggest new roles for DEK in nucleotide biosynthesis and ribosome formation, and in response to DNA replication stress.

Conclusions:

  • The DEK interactome model reveals diverse cellular pathway involvement for DEK.
  • DEK plays roles in de novo nucleotide biosynthesis and ribosome formation.
  • A DEK-RPA complex may form during DNA replication fork stalling.

Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

2.2K
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...
6.5K
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.6K
Protein Networks02:26

Protein Networks

2.9K
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...
3.4K