2022
DOI: 10.1016/j.jbc.2022.101890
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Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells

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Cited by 9 publications
(14 citation statements)
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“…Given our recent study demonstrating SpiD7 induces the UPR through crosslinking cellular proteins in ovarian cancer cell lines [10], we sought to confirm if SpiD3 generates unfolded/misfolded proteins in CLL cells. We used TPE-NMI; a thiol probe that fluoresces once bound to SEC groups on unfolded proteins [27].…”
Section: Spid3 Induces the Upr And Inhibits Protein Translation In Cllmentioning
confidence: 99%
See 1 more Smart Citation
“…Given our recent study demonstrating SpiD7 induces the UPR through crosslinking cellular proteins in ovarian cancer cell lines [10], we sought to confirm if SpiD3 generates unfolded/misfolded proteins in CLL cells. We used TPE-NMI; a thiol probe that fluoresces once bound to SEC groups on unfolded proteins [27].…”
Section: Spid3 Induces the Upr And Inhibits Protein Translation In Cllmentioning
confidence: 99%
“…Activated IRE1α splices XBP1 mRNA, which encodes a functional transcription factor that regulates genes involved in maintaining ER balance [8]. Cancer cells exhibit higher basal levels of unfolded proteins rendering them more vulnerable to UPR activation-induced apoptosis [9,10]. Several studies have shown that pharmacological inducers of the UPR promote CLL apoptosis in vitro [11,12].…”
Section: Introductionmentioning
confidence: 99%
“…To determine if any thiol-reactive compound can inactivate CitA by modifying C143, an in-house library of Michael acceptor containing compounds was tested in the CitA enzymatic assay. [42][43][44][45][46][47] These compounds were screened against 10 nM CitA at a concentration of 20 μM in the CitA enzymatic assay. Two of the 30 tested compounds were identified as hits by exhibiting a greater than 80% decrease in CitA activity.…”
Section: Modification Of the C143 Residue By Irreversible Michael Acc...mentioning
confidence: 99%
“…30,31 Subsequent studies using a biotinylated-analog 19 probe unveiled a proteome-wide target profile that identified over 330 proteins that are modified by analog 19. 32 This led to the discovery of spirocyclic dimers (SpiDs) as promising anticancer agents that inhibited cancer cell growth, and induced apoptosis through activation of unfolded protein response. 32,33 To assess MX's selectivity for RAD52 and to define the proteome-wide profile of MX, we synthesized a biotinylated-MX-probe (MXP).…”
mentioning
confidence: 99%
“…32 This led to the discovery of spirocyclic dimers (SpiDs) as promising anticancer agents that inhibited cancer cell growth, and induced apoptosis through activation of unfolded protein response. 32,33 To assess MX's selectivity for RAD52 and to define the proteome-wide profile of MX, we synthesized a biotinylated-MX-probe (MXP). In a proof-of-concept, we demonstrated that MXP indeed selectively binds to recombinant human RAD52 but not RPA in Escherichia coli lysates that have an abundance of these two proteins.…”
mentioning
confidence: 99%