Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome
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Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome. / Abildgaard, Amanda B.; Gersing, Sarah K.; Larsen-Ledet, Sven; Nielsen, Sofie V.; Stein, Amelie; Lindorff-Larsen, Kresten; Hartmann-Petersen, Rasmus.
In: Biomolecules, Vol. 10, No. 8, 1141, 2020.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome
AU - Abildgaard, Amanda B.
AU - Gersing, Sarah K.
AU - Larsen-Ledet, Sven
AU - Nielsen, Sofie V.
AU - Stein, Amelie
AU - Lindorff-Larsen, Kresten
AU - Hartmann-Petersen, Rasmus
PY - 2020
Y1 - 2020
N2 - Protein homeostasis (proteostasis) is essential for the cell and is maintained by a highly conserved protein quality control (PQC) system, which triages newly synthesized, mislocalized and misfolded proteins. The ubiquitin-proteasome system (UPS), molecular chaperones, and co-chaperones are vital PQC elements that work together to facilitate degradation of misfolded and toxic protein species through the 26S proteasome. However, the underlying mechanisms are complex and remain partly unclear. Here, we provide an overview of the current knowledge on the co-chaperones that directly take part in targeting and delivery of PQC substrates for degradation. While J-domain proteins (JDPs) target substrates for the heat shock protein 70 (HSP70) chaperones, nucleotide-exchange factors (NEFs) deliver HSP70-bound substrates to the proteasome. So far, three NEFs have been established in proteasomal delivery: HSP110 and the ubiquitin-like (UBL) domain proteins BAG-1 and BAG-6, the latter acting as a chaperone itself and carrying its substrates directly to the proteasome. A better understanding of the individual delivery pathways will improve our ability to regulate the triage, and thus regulate the fate of aberrant proteins involved in cell stress and disease, examples of which are given throughout the review.
AB - Protein homeostasis (proteostasis) is essential for the cell and is maintained by a highly conserved protein quality control (PQC) system, which triages newly synthesized, mislocalized and misfolded proteins. The ubiquitin-proteasome system (UPS), molecular chaperones, and co-chaperones are vital PQC elements that work together to facilitate degradation of misfolded and toxic protein species through the 26S proteasome. However, the underlying mechanisms are complex and remain partly unclear. Here, we provide an overview of the current knowledge on the co-chaperones that directly take part in targeting and delivery of PQC substrates for degradation. While J-domain proteins (JDPs) target substrates for the heat shock protein 70 (HSP70) chaperones, nucleotide-exchange factors (NEFs) deliver HSP70-bound substrates to the proteasome. So far, three NEFs have been established in proteasomal delivery: HSP110 and the ubiquitin-like (UBL) domain proteins BAG-1 and BAG-6, the latter acting as a chaperone itself and carrying its substrates directly to the proteasome. A better understanding of the individual delivery pathways will improve our ability to regulate the triage, and thus regulate the fate of aberrant proteins involved in cell stress and disease, examples of which are given throughout the review.
KW - chaperone
KW - co-chaperone
KW - misfolding
KW - proteasome
KW - protein quality control
KW - protein stability
KW - ubiquitin
U2 - 10.3390/biom10081141
DO - 10.3390/biom10081141
M3 - Review
C2 - 32759676
AN - SCOPUS:85089170937
VL - 10
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 8
M1 - 1141
ER -
ID: 247337191