KIAA0368-deficiency affects disassembly of 26S proteasome under oxidative stress condition

Kousuke Haratake1, Akitsugu Sato1, Fuminori Tsuruta1

  • 1Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.

Journal of Biochemistry
|January 24, 2016
PubMed

Insights

Extracellular mutants 29 (Ecm29) protein deficiency prevents 26S proteasome dissociation during cellular stress, enhancing protein degradation and oxidative stress resistance in mice.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular stress leads to intracellular protein damage, necessitating degradation via the ubiquitin-proteasome system.
  • The proteasome, a protease complex, comprises a 20S core and regulatory activators.
  • The function of Extracellular mutants 29 (Ecm29), a protein encoded by KIAA0368, in proteasome regulation remains largely unelucidated.

Purpose of the Study:

  • To investigate the role of Ecm29 (KIAA0368) in cellular stress response.
  • To determine the impact of Ecm29 deficiency on proteasome function under stress conditions.

Main Methods:

  • Generation of KIAA0368-deficient (KIAA0368(-/-)) mice.
  • Assessment of proteasome activity and integrity under normal and stressed conditions.
  • Evaluation of protein degradation efficiency and oxidative stress resistance in KIAA0368(-/-) cells.

Main Results:

  • KIAA0368(-/-) mice exhibited normal proteasome activity and formation under non-stressed conditions.
  • Unlike wild-type cells, 26S proteasome dissociation was inhibited in KIAA0368(-/-) cells under stress.
  • Ecm29 deficiency correlated with enhanced damaged protein degradation and increased resistance to oxidative stress.

Conclusions:

  • Ecm29 plays a crucial role in the dissociation of the 26S proteasome during cellular stress.
  • Ecm29 deficiency confers a protective advantage against oxidative stress by maintaining proteasome integrity.
  • This study provides insights into the mechanism of proteasomal degradation under diverse stress conditions.

Related Concept Videos

The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
2.1K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
2.0K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.5K
The Proteasome02:18

The Proteasome

5.0K
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
17.1K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.7K