ArticleCell stress & chaperones2004
Hsp70 mutant proteins modulate additional apoptotic pathways and improve cell survival.
Article in Cell stress & chaperones, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Molecular chaperones in stroke-induced immunosuppression.Neural regeneration research · 2023Article
- Involvement of histone methylation in the regulation of neuronal death.Journal of physiology and biochemistry · 2023Review
- Exploration of the truncated cytosolic Hsp70 in plants - unveiling the diverse T1 lineage and the conserved T2 lineage.Frontiers in plant science · 2023Article
- Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury.Cells · 2020Review
- Heat shock protein signaling in brain ischemia and injury.Neuroscience letters · 2020Review
- The Heat Shock Protein 70 Plays a Protective Role in Sepsis by Maintenance of the Endothelial Permeability.BioMed research international · 2020Article
- Characterizing the Neuroprotective Effects of S/B Remedy (Molecules (Basel, Switzerland) · 2019Article
- The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke.Expert opinion on therapeutic targets · 2018Review
- ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation.Nature communications · 2016Article
- Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and their therapeutic potential.Translational stroke research · 2013Review
- Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure brain and induce Hsp70 protein.Brain research · 2008Article
- Estimating residue evolutionary conservation by introducing von Neumann entropy and a novel gap-treating approach.Amino acids · 2008Article
- Article
- Extracellular heat shock protein 70: a critical component for motoneuron survival.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although wild-type Hsp70 (Hsp70WT) inhibits procaspase-3 processing by preventing apoptosome formation, Hsp70WT does not block active caspase-3. Because all caspase-3 inhibitors bear canonical DXXD caspase-3 recognition motifs, we determined whether mutated Hsp70s with caspase-binding motifs act as direct caspase-3 inhibitors. Based on Hsp70 molecular modeling, the DNQP, DEVQ, and EEVD regions localized on the surface of Hsp70WT were chosen, allowing us to design mutants while trying to avoid disrupting the global fold of the molecule and losing the possibility of protein-protein interactions. We replaced DNQP with DQMD, and DEVQ and EEVD with DEVD residues that should be optimal substrates for caspase-3. The resultant Hsp70 mutants directly interacted with active caspase-3 and blocked its proteolytic activity while retaining the ability to reverse protein denaturation and disrupt the interaction between Apaf-1 and procaspase-9. The Hsp70C-terminal mutants interacted with Apaf-1 and active caspase-3 significantly longer than Hsp70WT. The Hsp70 DXXD mutants protected neuron and teratocarcinoma (NT) cells against cell death much better than Hsp70WT whether given before or after serum withdrawal. Hsp70 mutants represent a possible approach to antiapoptotic biotherapeutics. Similar rational designs could be used to engineer inhibitors of additional caspase family members.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.