The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones
Abstract
:1. Introduction
2. Protein Folding and Molecular Chaperones
3. Molecular Chaperones Involved in Protein Folding and Protein Aggregate Reactivation
4. Interaction of Chaperones with Substrate Proteins and Protein Aggregates
5. Regulation of Chaperone Activity by Phosphorylation
5.1. Hsp40
5.2. Hsp110
5.3. Hsp70
5.3.1. Regulation of the Mitochondrial Redox Balance
5.3.2. Host-Pathogen Interaction
5.3.3. Regulation of Hsp70 Dimerization by Phosphorylation
5.3.4. Regulation of the Balance between Protein Folding and Degradation
5.3.5. Regulation of the Cell Cycle Progression
5.3.6. Hsp70 Phosphorylation Regulates Drug Resistance in Cancer Cells
5.3.7. Regulation of Apoptosis
6. Phosphorylation as Part of the Chaperone Code
6.1. How Phosphorylation Regulates the Conformation and Activity of These Chaperones?
6.2. How Phosphorylation Modulates Intermolecular Interactions?
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PTM | Posttranslational modifications |
Hsp | Heat shock protein |
PQC | Protein quality control |
NBD | Nucleotide binding domain |
SBD | Substrate binding domain |
CTD | C-terminal domain |
TLA | Three letter acronym |
ZBD | Zinc binding domain |
Apg | ATP and peptide-binding protein in germ cells |
EEVD | Glu-Glu-Val-Asp |
sHsp | Small heat shock protein |
αsyn | α-synuclein |
Htt | Huntingtin |
AS | Proline-rich acidic subdomain |
NEF | Nucleotide exchange factor |
TPR | Tetratricopeptide repeat |
MK5 | Mitogen-activated protein kinase-activated protein kinase 5 |
HSF1 | Heat shock factor 1 |
CSP | Cysteine string protein |
SNAP25 | Synaptosomal nerve-associated protein 25 |
PKC | Protein kinase C |
SOD2 | Superoxide dismutase-2 |
CHIP | C-terminus of Hsc70 interacting protein |
Akt1 | RAC-alpha serine/threonine-protein kinase |
UPS | Ubiquitin-proteasome system |
PP2C | Protein phosphatase 2C |
HOP | Hsp70/Hsp90 organizing protein |
CDK | Cyclin-dependent protein kinase |
G6PDH | Glucose 6 phosphate dehydrogenase |
Hsc | Heat shock cognate |
NMR | Nuclear magnetic resonance |
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Chaperone | Phosphorylation site(s) | Structural/Functional consequence(s) | Reference |
---|---|---|---|
hsDnaJB1 | Ser149, Ser151 and Ser171 | Inhibition of HSF1-mediated transcription | [86] |
hsCSP (DnaJC5) | Ser10 | Order-to-disorder transition. Modulation of neurotransmitter release by inhibiting binding to syntaxin and synaptotagmin | [87] |
hsCSP (DnaJC5) | Ser10 and Ser34 | Protection of the presynaptic terminal by promoting HSP70 chaperone activity | [88] |
hsHsp105α (HSPH1) | Ser509 | Inhibition of the Hsp105-induced suppression of Hsc70-mediated refolding | [89] |
hsHsp70 (HSPA1A) | Ser631 | Regulation of SOD2 import into the mitochondria and redox balance | [90] |
hsHsp70 (HSPA1A) | Tyr524 | Enhanced nuclear accumulation and heat-shock injury resistance | [91] |
hsHsc70 (HSPA8) | Thr495 | Inhibition of Hsp70 ATPase and refolding activities | [92] |
ecHsp70 (DnaK) | Thr504 | Stabilization of Hsp70 antiparallel dimers to position the client for transfer to Hsp90 | [93] |
hsHsc70 (HSPA8) | Thr636 | Enhanced interaction with HOP | [94] |
hsHsc70 (HSPA8) | Ser631 and Ser633 | Recruitment of Hsc70 to the centrosomes leading to mitotic spindle elongation and prevention of apoptosis | [95] |
scHsp70 (Ssa1) | Thr36 | Regulation of the cell cycle progression | [96] |
mmHsc70 (Hspa8) | Tyr288 | Cell uptake of methotrexate | [97] |
hsHsp70 (HSPA1A) | Ser486 | Inhibition of apoptosis | [98] |
hsHsp70 (HSPA1A) | Thr66 | Promotion of K-fiber assembly and mitotic progression | [99] |
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Velasco, L.; Dublang, L.; Moro, F.; Muga, A. The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones. Int. J. Mol. Sci. 2019, 20, 4122. https://doi.org/10.3390/ijms20174122
Velasco L, Dublang L, Moro F, Muga A. The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones. International Journal of Molecular Sciences. 2019; 20(17):4122. https://doi.org/10.3390/ijms20174122
Chicago/Turabian StyleVelasco, Lorea, Leire Dublang, Fernando Moro, and Arturo Muga. 2019. "The Complex Phosphorylation Patterns That Regulate the Activity of Hsp70 and Its Cochaperones" International Journal of Molecular Sciences 20, no. 17: 4122. https://doi.org/10.3390/ijms20174122