Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5

Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5

Protein homeostasis, including protein folding, refolding, and degradation, is thought to decline with aging. HSPB5 (also known as αB-crystallin) prevents target protein aggregation as a molecular chaperone and exhibits a cytoprotective function against various cell stresses. To elucidate the effect...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 23; no. 19; p. 11257
Main Authors: Ueda, Shuji, Nishihara, Moeka, Hioka, Yuuki, Yoshino, Ken-ichi, Yamada, Soichiro, Yamanoue, Minoru, Shirai, Yasuhito
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-10-2022
MDPI
Subjects:
Aging
Apoptosis
Biotin
Caspase-3
Cell cycle
Cellular stress response
Crystallin
Cytoplasm
desmin-related cardiomyopathy
Endoplasmic reticulum
ER stress
heat shock protein
Homeostasis
Kinases
Labeling
Localization
Mass spectrometry
Mass spectroscopy
MG132
Microscopy
Muscles
Musculoskeletal system
PARP
Peptides
Phosphorylation
PLK2
Polo-like kinase
Proteasome inhibitors
Protein folding
Protein interaction
Protein synthesis
Proteins
Scientific imaging
Serine
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Summary:Protein homeostasis, including protein folding, refolding, and degradation, is thought to decline with aging. HSPB5 (also known as αB-crystallin) prevents target protein aggregation as a molecular chaperone and exhibits a cytoprotective function against various cell stresses. To elucidate the effect of HSPB5 on endoplasmic reticulum (ER) stress, we searched for novel binding proteins of HSPB5 using the proximity-dependent biotin labeling method. Proteins presumed to interact with HSPB5 in cells treated with the proteasome inhibitor MG132 were identified by a reversible biotin-binding capacity method combining tamavidin2-REV magnetic beads and mass spectrometry. We discovered a new binding protein for HSPB5, polo-like kinase 2 (PLK2), which is an apoptosis-related enzyme. The expression of PLK2 was upregulated by MG132 treatment, and it was co-localized with HSPB5 near the ER in L6 muscle cells. Inhibition of PLK2 decreased ER stress-induced phosphorylation of serine 19 in HSPB5 and increased apoptosis by activation of caspase 3 under ER stress. Overexpression of HSPB5 (WT) suppressed the ER stress-induced caspase 3 activity, but this was not observed with phospho-deficient HSPB5 (3A) mutants. These results clarify the role of HSPB5 phosphorylation during ER stress and suggest that the PLK2/HSPB5 pathway plays an essential role in cytoprotection against proteasome inhibition-induced ER stress.
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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231911257