Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation

TY - JOUR

T1 - Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation

AU - Kriegenburg, Franziska

AU - Ellgaard, Lars

AU - Hartmann-Petersen, Rasmus

N1 - © 2011 The Authors Journal compilation © 2011 FEBS.

PY - 2012/2

Y1 - 2012/2

N2 - The accumulation of misfolded proteins presents a considerable threat to the health of individual cells and has been linked to severe diseases, including neurodegenerative disorders. Considering that, in nature, cells often are exposed to stress conditions that may lead to aberrant protein conformational changes, it becomes clear that they must have an efficient quality control apparatus to refold or destroy misfolded proteins. In general, cells rely on molecular chaperones to seize and refold misfolded proteins. If the native state is unattainable, misfolded proteins are targeted for degradation via the ubiquitin-proteasome system. The specificity of this proteolysis is generally provided by E3 ubiquitin-protein ligases, hundreds of which are encoded in the human genome. However, rather than binding the misfolded proteins directly, most E3s depend on molecular chaperones to recognize the misfolded protein substrate. Thus, by delegating substrate recognition to chaperones, E3s deftly utilize a pre-existing cellular system for selectively targeting misfolded proteins. Here, we review recent advances in understanding the interplay between molecular chaperones and the ubiquitin-proteasome system in the cytosol, nucleus, endoplasmic reticulum and mitochondria.

AB - The accumulation of misfolded proteins presents a considerable threat to the health of individual cells and has been linked to severe diseases, including neurodegenerative disorders. Considering that, in nature, cells often are exposed to stress conditions that may lead to aberrant protein conformational changes, it becomes clear that they must have an efficient quality control apparatus to refold or destroy misfolded proteins. In general, cells rely on molecular chaperones to seize and refold misfolded proteins. If the native state is unattainable, misfolded proteins are targeted for degradation via the ubiquitin-proteasome system. The specificity of this proteolysis is generally provided by E3 ubiquitin-protein ligases, hundreds of which are encoded in the human genome. However, rather than binding the misfolded proteins directly, most E3s depend on molecular chaperones to recognize the misfolded protein substrate. Thus, by delegating substrate recognition to chaperones, E3s deftly utilize a pre-existing cellular system for selectively targeting misfolded proteins. Here, we review recent advances in understanding the interplay between molecular chaperones and the ubiquitin-proteasome system in the cytosol, nucleus, endoplasmic reticulum and mitochondria.

U2 - 10.1111/j.1742-4658.2011.08456.x

DO - 10.1111/j.1742-4658.2011.08456.x

M3 - Journal article

C2 - 22177318

SN - 1742-464X

VL - 279

SP - 532

EP - 542

JO - F E B S Journal

JF - F E B S Journal

IS - 4

ER -