Source 1primary paper2024MED
Toolkit/stress granule inhibitory peptides
stress granule inhibitory peptides
Also known as: SIPs
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides
Usefulness & Problems
Why this is useful
SIPs are peptide inhibitors derived from stress granule core proteins and used to disrupt stress granules. The abstract presents them as anti-SG agents that can increase sorafenib sensitivity.; disrupting stress granule assembly; sensitizing cancer cells to sorafenib
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SIPs are peptide inhibitors derived from stress granule core proteins and used to disrupt stress granules. The abstract presents them as anti-SG agents that can increase sorafenib sensitivity.
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disrupting stress granule assembly
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sensitizing cancer cells to sorafenib
Problem solved
They address the problem that stress granules can support cancer cell survival and anticancer drug resistance. The paper positions SIPs as a way to improve efficacy of SG-inducing anticancer drugs.; providing a stress granule-targeting intervention to improve anticancer drug efficacy
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They address the problem that stress granules can support cancer cell survival and anticancer drug resistance. The paper positions SIPs as a way to improve efficacy of SG-inducing anticancer drugs.
Source:
providing a stress granule-targeting intervention to improve anticancer drug efficacy
Problem links
providing a stress granule-targeting intervention to improve anticancer drug efficacy
LiteratureThey address the problem that stress granules can support cancer cell survival and anticancer drug resistance. The paper positions SIPs as a way to improve efficacy of SG-inducing anticancer drugs.
Source:
They address the problem that stress granules can support cancer cell survival and anticancer drug resistance. The paper positions SIPs as a way to improve efficacy of SG-inducing anticancer drugs.
Published Workflows
Objective: Develop stress granule inhibitory peptides and evaluate whether they can overcome resistance to the SG-inducing anticancer drug sorafenib.
Why it works: The workflow pairs development of SG inhibitory peptides with identification of SG-inducing anticancer compounds and then tests whether SG disruption increases drug sensitivity.
disruption of stress granulespeptide engineeringcell-based screening
Stages
- 1.SG inhibitory peptide development(library_design)
This stage creates the peptide intervention candidates used to inhibit stress granules in cells.
Selection: Design peptides derived from Caprin1 and USP10 and fuse them with cell-penetrating peptides.
- 2.Cell-based screen for SG-inducing anticancer compounds(broad_screen)
This stage identifies drug contexts in which SG inhibition might be therapeutically useful.
Selection: Identify anticancer compounds that induce stress granules in cell-based screens.
- 3.Combination evaluation with sorafenib(confirmatory_validation)
This stage validates the therapeutic application of SIPs in a specific SG-inducing drug context.
Selection: Test whether SIPs can overcome resistance to the SG-inducing anticancer drug sorafenib.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
cell-penetrating peptide-mediated intracellular deliveryinhibition of stress granule assemblyTechniques
No technique tags yet.
Target processes
recombinationInput: Chemical
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
The reported constructs are fused to cell-penetrating peptides for use in cells. Their application is described in cell-based experiments with sorafenib in HeLa cells.; requires fusion to cell-penetrating peptides; application is described in the context of SG-inducing anticancer drugs
The abstract does not show that SIPs solve resistance broadly across cancers or in vivo. It also does not establish exact scope beyond the reported HeLa cell context.; abstract only reports testing in HeLa cells; exact peptide sequences and broader performance are not given in the abstract
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Stress granule inhibitory peptides increased the sensitivity of HeLa cells to sorafenib via disruption of stress granules.
We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs.
SG-inducing anticancer drugs could be combined with stress granule inhibitory peptides to sensitize cancer cells.
Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance.
The study developed stress granule inhibitory peptides derived from Caprin1 and USP10 and fused them to cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp.
Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug stress-granule-inhibitory-peptides
Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides
Source:
sensitization effectsupports
Stress granule inhibitory peptides increased the sensitivity of HeLa cells to sorafenib via disruption of stress granules.
We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs.
Source:
therapeutic strategysupports
SG-inducing anticancer drugs could be combined with stress granule inhibitory peptides to sensitize cancer cells.
Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance.
Source:
tool developmentsupports
The study developed stress granule inhibitory peptides derived from Caprin1 and USP10 and fused them to cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp.
Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively.
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Comparisons
Source-stated alternatives
The abstract contrasts SIP use with the broader underexplored area of chemical compounds targeting stress granules. It also frames combination with SG-inducing anticancer drugs as the therapeutic strategy.
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The abstract contrasts SIP use with the broader underexplored area of chemical compounds targeting stress granules. It also frames combination with SG-inducing anticancer drugs as the therapeutic strategy.
Source-backed strengths
explicitly designed to inhibit stress granules; reported to increase sorafenib sensitivity in HeLa cells
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explicitly designed to inhibit stress granules
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reported to increase sorafenib sensitivity in HeLa cells
Compared with H-2Kb-ADSCs
stress granule inhibitory peptides and H-2Kb-ADSCs address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; same primary input modality: chemical
Compared with inkube
stress granule inhibitory peptides and inkube address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; same primary input modality: chemical
Compared with synthetic multienzyme complexes
stress granule inhibitory peptides and synthetic multienzyme complexes address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; same primary input modality: chemical
Ranked Citations
- 1.