Affinage

GSPT1

Eukaryotic peptide chain release factor GTP-binding subunit ERF3A · UniProt P15170

Length
499 aa
Mass
55.8 kDa
Annotated
2026-06-10
62 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GSPT1 (eRF3a) is the major translation termination factor in human cells, functioning as a GTPase that partners with eRF1 to mediate stop codon recognition; depletion of eRF3a increases nonsense codon readthrough and destabilizes eRF1, establishing that eRF3a controls assembly of the termination complex by stabilizing its partner (PMID:15987998). Stoichiometry between the two factors is enforced by proteasomal quality control: eRF3a that is not bound to eRF1 is polyubiquitinated and degraded, so free eRF3a levels are adjusted to match eRF1 (PMID:18083835). Beyond canonical termination, eRF3a couples termination to mRNA fate through two overlapping PAM2 motifs that engage the MLLE domain of cytoplasmic PABP, with allelic glycine-repeat variation tuning this binding affinity (PMID:26818177), and its loss globally de-represses uORF-containing mRNAs through an NMD role largely non-overlapping with UPF1 (PMID:31619139). GSPT1 is proteolytically processed into a shorter isoform bearing an N-terminal IAP-binding motif that engages IAP proteins, promotes IAP ubiquitination and caspase activation, and drives apoptosis (PMID:12865429). GSPT1 also acts in cell proliferation, functioning downstream of Rac1 to drive astrocyte cell-cycle progression (PMID:27941025). Therapeutically, GSPT1 is recruited to the CRL4CRBN E3 ubiquitin ligase by cereblon-modulating molecular-glue compounds (CC-90009 and related CELMoDs), leading to its ubiquitination and proteasomal degradation, impaired translation termination, integrated stress response activation, and TP53-independent cancer cell death in leukemia and glioblastoma (PMID:35763353, PMID:29356495, PMID:39117611, PMID:33591756). GSPT1 additionally serves as a proviral host factor, physically associating with viral polymerases including Lassa virus polymerase and JEV NS5, such that its degradation suppresses viral infection (PMID:35858434, PMID:41471039).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established that the two mammalian eRF3 paralogs are functionally distinct, framing GSPT1/eRF3a as a non-interchangeable termination factor.

    Evidence Yeast SUP35 complementation with chimeric and deletion constructs of mouse GSPT1/GSPT2 plus human eRF1

    PMID:12354098

    Open questions at the time
    • Does not define the human cellular role of eRF3a versus eRF3b directly
    • The functional consequence of the GSPT1 84-120 region in mammalian cells is unresolved
  2. 2003 High

    Revealed a non-termination role: proteolytically processed GSPT1 acts as a pro-apoptotic IAP antagonist, answering whether eRF3 had functions beyond translation.

    Evidence Identification of processed isoform, IAP co-IP, caspase/IAP-ubiquitination assays, and IAP-binding motif mutagenesis

    PMID:12865429

    Open questions at the time
    • Protease and physiological trigger for processing not identified
    • In vivo relevance of the apoptotic isoform unestablished
  3. 2005 High

    Demonstrated that eRF3a, not eRF3b, is the major termination factor and stabilizes eRF1, defining the core mechanism of termination complex formation.

    Evidence siRNA depletion with nonsense codon readthrough reporter and eRF1 protein stability western blots

    PMID:15987998

    Open questions at the time
    • Structural basis of eRF1 stabilization not resolved
    • Does not address GTPase catalytic cycle directly
  4. 2007 High

    Explained how eRF3a/eRF1 stoichiometry is maintained: free eRF3a is polyubiquitinated and degraded, coupling complex assembly to protein turnover.

    Evidence eRF1-binding-site mutagenesis, MG132 proteasome inhibition, and polyubiquitination assays

    PMID:18083835

    Open questions at the time
    • E3 ligase responsible for free eRF3a degradation not identified
    • Cellular signals tuning this balance unknown
  5. 2014 Medium

    Linked GSPT1 to oncogenic signaling by showing it is a transcriptional effector of nicotine/EGF-ID1 signaling driving NSCLC proliferation and invasion.

    Evidence Microarray, siRNA knockdown, overexpression, and invasion/migration assays in NSCLC cells

    PMID:25028095

    Open questions at the time
    • Mechanism connecting GSPT1 termination activity to proliferation not defined
    • Direct ID1-GSPT1 promoter regulation indirectly inferred via co-repressor downregulation
  6. 2016 Medium

    Quantified how GSPT1 couples termination to deadenylation by mapping PAM2-MLLE binding and showing a cancer-associated allele alters PABP affinity.

    Evidence Surface plasmon resonance with allelic eRF3a N-terminal domains against PABP

    PMID:26818177

    Open questions at the time
    • Functional impact on deadenylation/translation in cells not shown
    • Single biophysical method
  7. 2016 High

    Placed GSPT1 downstream of Rac1 in a proliferation-specific signaling axis controlling astrocyte cell-cycle progression.

    Evidence Conditional Rac1 knockout mice, siRNA knockdown, GSPT1 overexpression rescue, and cell cycle/spinal cord injury models

    PMID:27941025

    Open questions at the time
    • Molecular link from Rac1 to GSPT1 expression unresolved
    • Whether the effect requires termination activity is unknown
  8. 2018 Medium

    Identified GSPT1 as a cereblon neosubstrate, showing molecular-glue degraders recruit it to CRL4CRBN for proteasomal degradation.

    Evidence Quantitative chemical proteomics, molecular docking into the CRBN-GSPT1 interface, and leukemia viability assays

    PMID:29356495

    Open questions at the time
    • Initially an off-target finding; selectivity over other neosubstrates not fully defined here
    • No high-resolution structure of the ternary complex
  9. 2019 Medium

    Defined the global mRNA consequences of GSPT1 loss, showing de-repression of uORF-containing transcripts and an NMD role largely distinct from UPF1.

    Evidence RNA-seq and ribosome profiling after siRNA knockdown of eRF3A versus UPF1

    PMID:31619139

    Open questions at the time
    • Mechanism of uORF-specific regulation not resolved
    • Overlap with other termination/NMD factors not mapped
  10. 2021 Medium

    Advanced GSPT1 degradation to a clinical-stage strategy by characterizing CC-90009 as a selective CRL4CRBN-mediated GSPT1 degrader for AML.

    Evidence Quantitative proteomics, cell degradation assays, pharmacokinetics, and in vivo efficacy models

    PMID:33591756

    Open questions at the time
    • Downstream death pathway not fully dissected in this report
    • Resistance mechanisms not addressed
  11. 2022 High

    Mechanistically connected GSPT1 degradation to impaired termination, ISR activation, and TP53-independent leukemic death, and engineered a Crbn knockin sparing hematopoietic stem cells for in vivo study.

    Evidence Genome-wide CRISPR screens, Crbn domain-mapping, knockin mouse model, and ISR marker readouts

    PMID:35763353

    Open questions at the time
    • Precise trigger linking termination defect to ISR not fully defined
    • Why high translation rate sensitizes cells remains mechanistically open
  12. 2022 Medium

    Extended therapeutic logic to nonsense-mutation diseases, showing eRF3a degraders promote CFTR premature-termination-codon readthrough.

    Evidence CFTR ion transport and Ussing chamber assays in airway epithelial cells with eRF3a degraders, alone and with G418

    PMID:35900863

    Open questions at the time
    • ENaC off-effect could limit therapeutic window
    • Readthrough efficiency remains submaximal
  13. 2022 Medium

    Established GSPT1 as a proviral host factor by showing physical association with Lassa virus polymerase and antiviral effect of its degradation.

    Evidence TurboID proximity proteomics, siRNA screen, and CC-90009 degrader treatment in LASV infection assays

    PMID:35858434

    Open questions at the time
    • Direct binding versus proximity not distinguished
    • Mechanism of polymerase support undefined
  14. 2022 Medium

    Demonstrated GSPT1 is essential for glioblastoma survival and a degradation target in that tumor type.

    Evidence CRISPR knockout with rescue, in vivo xenograft survival, and cleaved-PARP1 apoptosis assays with CC-885

    PMID:39117611

    Open questions at the time
    • Whether dependence reflects termination activity specifically is unclear
    • ISR involvement in GBM not directly tested
  15. 2025 Medium

    Provided a mechanistic basis for combination therapy by showing GSPT1 loss preferentially reduces translation of short-half-life proteins like c-Myc, synergizing with IRAK4 inhibition.

    Evidence Proteomics and c-Myc protein stability western blots in AML cell lines and primary samples

    PMID:40670672

    Open questions at the time
    • Generalizability beyond c-Myc not fully mapped
    • Quantitative contribution of termination versus initiation effects unresolved
  16. 2025 Low

    Implicated GSPT1 degradation in disrupting leukemic fusion-driven transcriptional networks in pediatric AML.

    Evidence CC-90009 and CDK6-PROTAC treatment with western blot and RT-PCR for fusion transcripts in AML cells

    PMID:39857993

    Open questions at the time
    • Pharmacological degradation without genetic rescue to confirm specificity
    • Direct versus indirect effect on fusion transcription not separated
  17. 2025 Low

    Proposed mitochondrial-quality-control involvement, linking GSPT1 to Parkin ubiquitination and compensatory mitophagy in lung adenocarcinoma.

    Evidence RNA immunoprecipitation, cycloheximide chase, LC3 mitophagy reporter, electron microscopy, and xenograft rescue of TMEM106C silencing

    PMID:42167422

    Open questions at the time
    • Mechanism by which GSPT1 promotes Parkin ubiquitination is indirect
    • Not independently confirmed
  18. 2025 Medium

    Extended antiviral degrader strategy to flaviviruses, showing GSPT1 interacts with JEV NS5 and its CC-90009-mediated degradation suppresses infection.

    Evidence Co-immunoprecipitation, siRNA knockdown, CC-90009 treatment, and an in vivo murine JEV model

    PMID:41471039

    Open questions at the time
    • Direct binding interface with NS5 not mapped
    • Role in viral translation versus replication not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GSPT1 degradation mechanistically triggers the integrated stress response and selectively kills cancer cells, and whether its non-termination roles (apoptosis, proliferation signaling, mitophagy) depend on its termination activity, remain open.
  • Causal link from termination defect to ISR/eIF2alpha signaling not defined
  • Structural model of the CRBN-GSPT1 ternary complex not in corpus
  • Integration of GTPase, apoptotic, and signaling functions unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 2 GO:0045182 translation regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2
Partners
BIRC2CRBNETF1PABPC1RAC1
Complex memberships
CRL4CRBN E3 ubiquitin ligase (neosubstrate)eRF1-eRF3a translation termination complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 eRF3a/GSPT1 (but not eRF3b) is the major translation termination factor in human cells: siRNA-mediated depletion of eRF3a caused a significant increase in readthrough at a premature nonsense codon, while eRF3b depletion had no significant effect. eRF3a depletion also reduced intracellular eRF1 protein levels by decreasing its stability, demonstrating that eRF3a controls formation of the translation termination complex by stabilizing eRF1. siRNA knockdown, reporter readthrough assay, western blot for eRF1 stability Molecular and cellular biology High 15987998
2007 eRF3a/GSPT1 is degraded by the proteasome when not associated with eRF1. eRF3a mutants altered in the eRF1-binding site showed decreased stability that was rescued by the proteasome inhibitor MG132, and both mutant and wild-type eRF3a were found to be polyubiquitinated. This proteasomal degradation of free eRF3a adjusts eRF3a levels to match eRF1 levels, thereby controlling translation termination complex formation. Mutagenesis of eRF1-binding site, proteasome inhibitor (MG132) treatment, polyubiquitination assay, western blot RNA (New York, N.Y.) High 18083835
2003 GSPT1/eRF3 is proteolytically processed into a shorter isoform that harbors a conserved N-terminal IAP-binding motif (AKPF). The processed isoform interacts biochemically with IAP proteins, promotes caspase activation, IAP ubiquitination, and apoptosis. The IAP-binding motif is absolutely required for these activities. Identification of processed isoform, biochemical pulldown/co-IP with IAPs, caspase activation assay, IAP ubiquitination assay, mutagenesis of IAP-binding motif The Journal of biological chemistry High 12865429
2016 eRF3a/GSPT1 N-terminal glycine repeat influences binding affinity to PABP (cytoplasmic poly(A) binding protein) via two overlapping PAM2 motifs that recognize the MLLE domain of PABP. The cancer-associated 12-GGC allele (encoding 12 glycines) has decreased binding affinity for PABP compared to the common 10-GGC allele, as measured by surface plasmon resonance, suggesting that this allele could modify coupling between translation termination and mRNA deadenylation. Surface plasmon resonance (SPR) binding assay with allelic forms of eRF3a N-terminal domain and PABP or poly(A)-bound PABP RNA biology Medium 26818177
2002 Mouse GSPT2 but not GSPT1 can functionally substitute for the essential yeast eRF3 gene SUP35 in vivo. The region spanning amino acids 84-120 of mGSPT1 prevents complementation of the sup35 mutation, but this region alone is insufficient to block complementation; the full-length mGSPT1 context is required. Complementation was achieved with mGSPT2 co-expressed with human eRF1 but not with mGSPT1 and human eRF1, indicating the two mammalian paralogs are functionally distinct. Yeast genetic complementation of SUP35 deletion, N-terminal deletion constructs, chimeric protein analysis Genes to cells : devoted to molecular & cellular mechanisms High 12354098
2016 A novel Rac1-GSPT1 signaling axis controls astrocyte proliferation in the context of inflammation and CNS injury. Rac1 knockout or knockdown in astrocytes decreased GSPT1 expression and reduced cell cycle progression; overexpression of GSPT1 rescued the cell cycle delay induced by Rac1 knockdown. GSPT1-KD astrocytes showed cell cycle delay but no effect on cell migration, placing GSPT1 downstream of Rac1 in the proliferation (but not migration) arm of astrogliosis signaling. Conditional Rac1 knockout mice (GFAP-Cre;Rac1flox/flox), siRNA knockdown, overexpression rescue, cell cycle analysis, in vivo spinal cord injury model The Journal of biological chemistry High 27941025
2022 GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response (ISR) pathway, and TP53-independent cell death in leukemia cells. CRISPR/Cas9 screens identified decreased translation initiation as protective following GSPT1 degradation, suggesting cells with higher translation rates are more susceptible. Two specific Crbn amino acids in mice prevent Gspt1 degradation by the molecular glue drugs, which was confirmed in a knockin mouse model that enabled in vivo efficacy studies while sparing hematopoietic stem cells. CRISPR/Cas9 screens, domain-mapping experiments, knockin mouse model, flow cytometry, western blot for ISR markers The Journal of clinical investigation High 35763353
2022 GSPT1/eRF3a physically associates with Lassa virus polymerase, identified by proximity proteomics (TurboID), and functions as a proviral host factor. siRNA knockdown of GSPT1 inhibited authentic LASV infection, and targeted degradation of GSPT1 by CC-90009 strongly inhibited LASV infection in cultured cells. Proximity proteomics (TurboID biotin ligase fusion), siRNA screen, small-molecule degrader treatment, plaque/infection assay Proceedings of the National Academy of Sciences of the United States of America Medium 35858434
2022 eRF3a/GSPT1 degraders (cereblon E3 ligase modulators) rescue W1282X-CFTR premature termination codon function to ~20% of WT levels by promoting PTC readthrough; when paired with G418, they rescue G542X-CFTR function to ~50% of WT. eRF3a degraders also diminished epithelial sodium channel (ENaC) function. CFTR ion transport assays in airway epithelial cell lines, small-molecule eRF3a degrader treatment, Ussing chamber electrophysiology The Journal of clinical investigation Medium 35900863
2019 eRF3A/GSPT1 depletion globally de-represses expression of mRNAs containing translated upstream open reading frames (uORFs) while having opposing effects on ribosome protein gene expression compared to UPF1 knockdown. Less than 250 transcripts were targeted by both eRF3A and UPF1, demonstrating that their roles in NMD are largely non-overlapping. RNA sequencing, ribosome profiling, siRNA knockdown of eRF3A and UPF1 in human cells RNA biology Medium 31619139
2018 GSPT1 is recruited to the CRL4CRBN (CUL4-RBX1-DDB1-CRBN) E3 ubiquitin ligase by small-molecule phthalimide degraders, resulting in its ubiquitination and proteasomal degradation. This was identified as an off-target event independent of the targeting ligand in the bifunctional degrader molecules, confirmed by orthogonal target identification and molecular docking into the CRBN-GSPT1 interface. Quantitative chemical proteomics, molecular docking, cell viability assays in leukemia lines ACS chemical biology Medium 29356495
2022 GSPT1 degradation by cereblon modulator CC-885 is effective against glioblastoma in vivo. GSPT1-knockout U87 glioblastoma cells showed enhanced apoptosis (as measured by cleaved PARP1), and mice transplanted with GSPT1-KO cells had significantly longer survival than WT controls; rescue by re-expression of GSPT1 reversed the survival benefit, establishing that GSPT1 is essential for glioblastoma cell survival. GSPT1 CRISPR/Cas9 knockout, rescue overexpression, in vivo xenograft survival model, cleaved PARP1 apoptosis assay Cell death & disease Medium 39117611
2021 CC-90009 is a cereblon E3 ligase modulating drug that specifically targets GSPT1 for proteasomal degradation via the CRL4CRBN complex, representing the first CELMoD to enter clinical development for this mechanism in AML. Quantitative proteomics, cell-based degradation assays, pharmacokinetic characterization, in vivo efficacy models Journal of medicinal chemistry Medium 33591756
2014 GSPT1 is induced by nicotine and EGF in an ID1-dependent manner in NSCLC cells. ID1 induces GSPT1 at the transcriptional level by downregulating two transcriptional co-repressors, NRSF and ZBP89. Depletion of GSPT1 abrogated nicotine-induced proliferation, invasion, and migration of NSCLC cells. Microarray, siRNA knockdown, overexpression, RT-PCR, invasion/migration assays Molecular cancer Medium 25028095
2022 eRF3a (GSPT1) overexpression promotes proliferation and migration of liver cancer cells through activation of the ERK and JNK signaling pathways, as determined by western blot analysis of pathway markers upon eRF3a overexpression. Overexpression in liver cancer cell lines, CCK8, colony formation, Transwell assay, western blot for ERK/JNK pathway markers Current medical science Low 34985612
2025 GSPT1 senses the stop codon of MYC mRNA to promote MYC translation, and MYC in turn promotes transcription of GSPT1, establishing a co-regulatory positive feedback loop. Dual MYC/GSPT1 protein degradation by GT19630 activates the integrated stress response, abrogates oxidative phosphorylation via inhibition of the TCA cycle, and induces TP53-independent cell death. Reporter assays for MYC translation, transcriptional analysis, dual degrader treatment, ISR marker analysis, metabolomics (TCA cycle), xenograft models bioRxiv (PREPRINT)preprint Low
2025 GSPT1 loss reduces translation efficiency particularly for proteins with short half-lives such as c-Myc. GSPT1 degradation in IRAK4-inhibited leukemic cells leads to accelerated c-Myc protein loss due to decreased protein stability, providing a mechanistic basis for synergy between IRAK4 inhibitors and GSPT1-targeting CELMoDs. Transcriptional and proteomic analyses, western blot for c-Myc protein stability, AML cell lines, primary patient samples Leukemia Medium 40670672
2025 GSPT1 degradation impairs expression of leukemic fusion gene transcripts (RUNX1::RUNX1T1 and FUS::ERG) and their cooperating transcription factors RUNX1 and ERG in pediatric AML cells, revealing a novel role for GSPT1 in regulating leukemic transcriptional networks. CC-90009 and CDK6-PROTAC (GU3341) treatment, western blot, RT-PCR for fusion transcripts, in vitro and ex vivo AML cell experiments Cancers Low 39857993
2025 GSPT1 promotes Parkin ubiquitination and is associated with altered Parkin turnover under mitochondrial stress, thereby enhancing compensatory mitophagy in lung adenocarcinoma cells. GSPT1 overexpression reversed the inhibitory effects of TMEM106C silencing on cancer growth and restored mitophagy. RNA immunoprecipitation, cycloheximide chase, GFP-mRFP-LC3 mitophagy assay, transmission electron microscopy, western blot for autophagy markers, xenograft model International journal of biological macromolecules Low 42167422
2025 CC-90009-mediated degradation of GSPT1 inhibits Japanese encephalitis virus (JEV) infection by disrupting viral translation and replication. Co-immunoprecipitation confirmed that GSPT1 physically interacts with the JEV non-structural protein NS5, and CC-90009 induces proteasomal degradation of the GSPT1/NS5 complex. Co-immunoprecipitation, siRNA knockdown of GSPT1, CC-90009 treatment, JEV infection assay, viral RNA and protein quantification, in vivo murine JEV model Pharmaceutics Medium 41471039

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders. ACS chemical biology 143 29356495
2021 CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia. Journal of medicinal chemistry 115 33591756
2021 Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators. Journal of medicinal chemistry 84 34042448
2003 The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. The Journal of biological chemistry 80 12865429
2015 miRNA-144 suppresses proliferation and migration of colorectal cancer cells through GSPT1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 76 26349975
2005 Involvement of human release factors eRF3a and eRF3b in translation termination and regulation of the termination complex formation. Molecular and cellular biology 75 15987998
2020 Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library. ACS chemical biology 67 32865967
2017 Protein Degradation via CRL4CRBN Ubiquitin Ligase: Discovery and Structure-Activity Relationships of Novel Glutarimide Analogs That Promote Degradation of Aiolos and/or GSPT1. Journal of medicinal chemistry 57 28358507
2022 Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells. The Journal of clinical investigation 54 35763353
2019 LncRNA DLX6-AS1 promotes the proliferation, invasion, and migration of non-small cell lung cancer cells by targeting the miR-27b-3p/GSPT1 axis. OncoTargets and therapy 41 31190891
2005 Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility. Carcinogenesis 41 15987717
2005 Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types. Journal of clinical pathology 39 15917414
2022 Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma. Cancer letters 37 35839920
2016 A Novel Rac1-GSPT1 Signaling Pathway Controls Astrogliosis Following Central Nervous System Injury. The Journal of biological chemistry 36 27941025
2014 Nicotine-mediated invasion and migration of non-small cell lung carcinoma cells by modulating STMN3 and GSPT1 genes in an ID1-dependent manner. Molecular cancer 33 25028095
2023 Structural rationalization of GSPT1 and IKZF1 degradation by thalidomide molecular glue derivatives. RSC medicinal chemistry 32 36970148
2022 Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough. The Journal of clinical investigation 31 35900863
2022 SJPYT-195: A Designed Nuclear Receptor Degrader That Functions as a Molecular Glue Degrader of GSPT1. ACS medicinal chemistry letters 31 35978691
2023 The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia. Blood 29 37172201
2009 Differential expression of GSPT1 GGCn alleles in cancer. Cancer genetics and cytogenetics 26 19963113
2019 Downregulation of microRNA-27b-3p via aberrant DNA methylation contributes to malignant behavior of gastric cancer cells by targeting GSPT1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 31539861
2002 Mouse GSPT2, but not GSPT1, can substitute for yeast eRF3 in vivo. Genes to cells : devoted to molecular & cellular mechanisms 23 12354098
2022 Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals. Proceedings of the National Academy of Sciences of the United States of America 21 35858434
2020 Long Non-coding RNA MINCR Regulates miR-876-5p/GSPT1 Axis to Aggravate Glioma Progression. Neurochemical research 18 32333234
1992 Mapping of the human GSPT1 gene, a human homolog of the yeast GST1 gene, to chromosomal band 16p13.1. Somatic cell and molecular genetics 18 1574740
2022 Structure-activity relationship analysis of novel GSPT1 degraders based on benzotriazinone scaffold and its antitumor effect on xenograft mouse model. Bioorganic chemistry 17 35717803
2021 Long non-coding RNA LINC00511 promotes proliferation, invasion, and migration of non-small cell lung cancer cells by targeting miR-625-5p/GSPT1. Translational cancer research 17 35116366
2011 GGCn polymorphism of eRF3a/GSPT1 gene and breast cancer susceptibility. Medical oncology (Northwood, London, England) 17 22101789
2007 Proteasomal degradation of human release factor eRF3a regulates translation termination complex formation. RNA (New York, N.Y.) 16 18083835
2018 The role of miR-144/GSPT1 axis in gastric cancer. European review for medical and pharmacological sciences 14 30024602
2024 Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective. Medicinal research reviews 13 38314926
2023 Discovery of new Lenalidomide derivatives as potent and selective GSPT1 degraders. European journal of medicinal chemistry 12 37418973
2022 GSPT1 Functions as a Tumor Promoter in Human Liver Cancer. Current medical science 12 36459303
2016 Studies on human eRF3-PABP interaction reveal the influence of eRF3a N-terminal glycin repeat on eRF3-PABP binding affinity and the lower affinity of eRF3a 12-GGC allele involved in cancer susceptibility. RNA biology 12 26818177
2019 Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes. RNA biology 11 31619139
2024 Identification of novel GSPT1 degraders by virtual screening and bioassay. European journal of medicinal chemistry 10 38795517
2025 Discovery of degrader for FLT3, GSPT1 and IKZF1/3 proteins merging PROTAC and molecular glue targeting FLT3-ITD mutant acute myeloid leukemia. European journal of medicinal chemistry 9 40578254
2025 Discovery of highly potent dual GSPT1/BRD4 degraders with anti-AML activity. European journal of medicinal chemistry 8 39965406
2025 Design and Discovery of Preclinical Candidate LYG-409 as a Highly Potent and Selective GSPT1 Molecular Glue Degraders. Journal of medicinal chemistry 7 39854008
2025 Cancer Biology of GSPT1: Mechanisms and Targeted Therapy Opportunities of Molecular Glue Degraders. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 6 41194439
2024 Potential of GSPT1 as a novel target for glioblastoma therapy. Cell death & disease 6 39117611
2025 PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia. Cancers 5 39857993
2025 Discovery of a novel molecular glue degrader targeting GSPT1/2 with a non-IMiD-based CRBN binder. European journal of medicinal chemistry 4 40252382
2025 Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization. Leukemia 4 40670672
2025 GSPT1 degraders: research progress, development strategies and challenges. Bioorganic & medicinal chemistry 4 41004880
2023 Hsa_circ_0001944 enhanced GSPT1 expression via sponging miR-498 to promote proliferation and invasion of gastric cancer. Journal of clinical laboratory analysis 4 36597856
2022 Overexpression of eRF3a Promotes Cell Proliferation and Migration in Liver Cancer. Current medical science 4 34985612
2025 Targeting MYC for the treatment of breast cancer: use of the novel MYC-GSPT1 degrader, GT19630. Investigational new drugs 3 39875774
2025 Evaluation of anti-leukemic activity and underlying mechanisms of the novel GSPT1 degrader AB138 in acute myeloid leukemia. Investigational new drugs 3 40366532
2025 Characterization of a dual degrader of MDM2 and GSPT1. European journal of medicinal chemistry 3 40440791
2025 High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader. Experimental hematology & oncology 3 40551250
2025 Targeted degradation of GSPT1 and NEK7 by a molecular glue prodrug for treatment of HCC. Communications chemistry 3 40813917
2023 MicroRNA-508-3p regulates the proliferation of human lung cancer cells by targeting G1 to S phase transition 1 (GSPT1) protein. Acta biochimica Polonica 3 38099479
2026 Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1. Asian journal of pharmaceutical sciences 1 41810469
2025 Novel eRF3a degrader enhances gentamicin-induced premature termination codon readthrough in epidermolysis bullosa. Molecular therapy. Nucleic acids 1 41210582
2025 Discovery of a dual-target CRBN-mediated degrader for IKZF1/3 and GSPT1 proteins. Bioorganic chemistry 1 41411691
2025 CC-90009, a Cereblon E3 Ligase Modulator, Exhibits Antiviral Efficacy Against JEV In Vitro and In Vivo via Targeted Degradation of GSPT1 and Viral NS5 Protein. Pharmaceutics 1 41471039
2026 Design synthesis and biological evaluation of novel BCL6/GSPT1 degrader as anti-DLBCL agent. European journal of medicinal chemistry 0 41529442
2026 GSPT1-specific protein degradation is effective in preclinical models of chemoresistant MYCN-amplified neuroblastoma. Journal of experimental & clinical cancer research : CR 0 41652432
2026 Synthesis and biological evaluation of Retro-2-based PROTACs reveal PEG-linker length and warhead impact on GSPT1 degradation. European journal of medicinal chemistry 0 41672026
2026 Transmembrane protein 106C promotes lung adenocarcinoma progression through GSPT1-mediated compensatory mitophagy. International journal of biological macromolecules 0 42167422
2025 Identification of potent and orally bioavailable GSPT1 molecular glue degraders. Bioorganic & medicinal chemistry letters 0 40825410

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