Affinage

SIAH1

E3 ubiquitin-protein ligase SIAH1 · UniProt Q8IUQ4

Length
282 aa
Mass
31.1 kDa
Annotated
2026-06-10
100 papers in source corpus 54 papers cited in narrative 54 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SIAH1 is a RING-domain E3 ubiquitin ligase that controls the abundance of a broad set of signaling, transcriptional, and cytoskeletal proteins by directing them to the proteasome, thereby intersecting Wnt, hypoxia, DNA-damage, and apoptotic pathways (PMID:9858595, PMID:18536714). Its catalytic activity requires the N-terminal RING domain—mutations there abolish substrate proteolysis and stabilize SIAH1 itself, which otherwise undergoes proteasomal self-degradation—while C-terminal sequences mediate oligomerization and substrate binding (PMID:9858595). SIAH1 functions as a homodimer presenting an electronegative substrate-engaging surface, and can assemble into an SCF-like complex with the adaptor SIP/CacyBP, Skp1, and the F-box protein Ebi to mediate phosphorylation-independent, beta-TrCP-independent degradation of beta-catenin, linking p53 activation to suppression of TCF/LEF transcription (PMID:11389839, PMID:11389840, PMID:12421809, PMID:16085652, PMID:20181957). Through this ubiquitin-ligase activity SIAH1 targets numerous substrates including HIPK2, the elongation factors ELL1/ELL2 within the super elongation complex, EB3 and the chromokinesin Kid during mitosis, Numb, Akt3, YAP, MyD88, FIH, TRB3, CPSF1, and YBX-1 (PMID:18536714, PMID:22483617, PMID:19696028, PMID:11146551, PMID:11752454, PMID:31471318, PMID:35723276, PMID:32117091, PMID:17188242, PMID:18276110, PMID:35402071, PMID:35273154). A distinct non-degradative mode is seen with alpha-synuclein, where SIAH1 together with the E2 UbcH8 catalyzes mono- and di-ubiquitination that promotes aggregation and toxicity rather than turnover, while it degrades the related protein synphilin-1 (PMID:18065497, PMID:14506261). Substrate selection and ligase output are tuned by post-translational modification of substrates and competitor proteins: phosphorylation of EB3, YAP, and SIAH1 itself (ATM/ATR-dependent Ser-19, ASK1-dependent Thr residues) gate complex formation, and TBL1, HCF1/2, and B23/nucleophosmin block substrate access or catalysis (PMID:18536714, PMID:19696028, PMID:25391652, PMID:20181957, PMID:32479599, PMID:23027902). A separate, catalysis-dependent role couples SIAH1 to stress signaling and cell death: S-nitrosylated GAPDH binds SIAH1 and is escorted to the nucleus where it stabilizes SIAH1 to drive degradation of nuclear targets and apoptosis, a cascade implicated in hyperglycemic and excitotoxic cell death (PMID:15951807, PMID:23027902, PMID:19940145, PMID:26438826). SIAH1 also promotes mitophagy when recruited to mitochondria (PMID:27334109, PMID:36385558). Its own transcription is induced by E2F1 and by HIF-1alpha acting with KDM3A, and repressed by EHMT2-mediated H3K9 methylation (PMID:20187294, PMID:28843785, PMID:21847359).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established that SIAH1 is a self-regulating RING-dependent E3 ligase, defining the catalytic module (N-terminal RING) versus the substrate/oligomerization module (C-terminus) that organizes all later mechanism.

    Evidence Domain mutagenesis, Co-IP, proteasome inhibitor and antisense assays on DCC degradation

    PMID:9858595

    Open questions at the time
    • Did not define the E2 partner
    • Substrate repertoire beyond DCC unknown at the time
  2. 2000 Medium

    Extended SIAH1 substrate control to mitotic machinery, showing it degrades the chromokinesin Kid and associates with alpha-tubulin during mitosis.

    Evidence Yeast two-hybrid, Co-IP, RING-deletion degradation assays

    PMID:11146551

    Open questions at the time
    • No in vitro reconstituted ubiquitination
    • Physiological consequence of Kid turnover only inferred from overexpression
  3. 2001 High

    Defined a major signaling output—phosphorylation-independent destruction of beta-catenin—through an SCF-like SIAH1/SIP/Skp1/Ebi complex assembled downstream of p53, connecting genotoxic stress to Wnt pathway shutdown.

    Evidence Reciprocal Co-IP, co-expression degradation, yeast two-hybrid, Xenopus microinjection across two concurrent papers

    PMID:11389839 PMID:11389840

    Open questions at the time
    • Mechanism of substrate recognition without phospho-degron unresolved
    • Relative contribution of APC interaction versus SCF complex unclear
  4. 2002 High

    Provided the structural basis for SIAH1 dimerization and adaptor engagement, showing an electronegative dimer-interface surface required for SIP binding.

    Evidence Structure-based analysis with site-directed mutagenesis and binding assays

    PMID:12421809

    Open questions at the time
    • No structure of a bound degron substrate
    • Did not resolve how diverse substrates dock the same surface
  5. 2003 High

    Distinguished SIAH1's substrate selectivity within Parkinson's-relevant proteins, degrading synphilin-1 (relieving its inhibition of dopamine release) but not alpha-synuclein under those conditions.

    Evidence Yeast two-hybrid, brain Co-IP, ubiquitination and dopamine-release assays

    PMID:14506261

    Open questions at the time
    • Conditions permitting alpha-synuclein handling not yet defined
    • In vivo relevance to neurodegeneration not shown
  6. 2005 High

    Uncovered a redox-controlled apoptotic axis: S-nitrosylated GAPDH binds SIAH1, which provides the nuclear import signal and is reciprocally stabilized, enabling nuclear substrate degradation and cell death.

    Evidence Reciprocal Co-IP, S-nitrosylation assays, nuclear fractionation, NO-deletion genetics in macrophages and neurons

    PMID:15951807

    Open questions at the time
    • Identity of the critical nuclear substrates driving death incompletely mapped
    • Quantitative contribution of GAPDH stabilization versus other inputs unclear
  7. 2005 High

    Resolved how the SIP adaptor bridges SIAH1 to Skp1, defining two structural elements both required for beta-catenin destruction.

    Evidence X-ray crystallography, NMR, mutagenesis, cell-based beta-catenin degradation

    PMID:16085652

    Open questions at the time
    • Did not capture beta-catenin within the complex
    • F-box/Ebi positioning not structurally resolved
  8. 2007 High

    Revealed a non-degradative ubiquitination mode in which SIAH1 with UbcH8 mono/di-ubiquitinates alpha-synuclein to promote aggregation rather than turnover, with disease mutations differentially affected.

    Evidence In vivo ubiquitination, aggregation assays, A30P/A53T mutagenesis

    PMID:18065497

    Open questions at the time
    • Structural determinant selecting mono/di- versus poly-ubiquitination unknown
    • In vivo aggregation consequence not tested in animal models
  9. 2008 High

    Showed SIAH1 activity is gated by DNA-damage signaling: ATM/ATR phosphorylation of Ser-19 dissociates the HIPK2 complex to stabilize HIPK2 and switch cells between recovery and apoptosis.

    Evidence Co-IP, ubiquitination assay, Ser-19 mutagenesis, ATM/ATR inhibition, siRNA

    PMID:18536714

    Open questions at the time
    • Direct kinase-substrate phosphorylation not reconstituted in vitro
    • Other phospho-regulated substrate complexes not surveyed
  10. 2009 High

    Demonstrated phospho-gating of a mitotic substrate, with Aurora-A/B phosphorylation of EB3 disrupting the SIAH1 complex to stabilize EB3 for prometaphase progression.

    Evidence Ubiquitination assay, phospho-site mutagenesis, cell cycle analysis, siRNA

    PMID:19696028

    Open questions at the time
    • Whether SIAH1 acts on EB3 in interphase unclear
    • Connection to the alpha-tubulin/Kid mitotic roles not integrated
  11. 2010 High

    Proved SIAH1 alone is a sufficient beta-catenin ligase in vitro and identified competitive protection by TBL1 binding the same armadillo repeats during Wnt signaling.

    Evidence In vitro ubiquitination with purified components, Co-IP, competition assays

    PMID:20181957

    Open questions at the time
    • Reconciliation of homodimer-sufficient activity with the SCF-like complex requirement
    • Stoichiometry of TBL1 competition in vivo not quantified
  12. 2012 High

    Identified a nitrosylation-dependent brake on SIAH1, with trans-nitrosylated B23/nucleophosmin disrupting the GAPDH-SIAH1 complex and abrogating ligase activity to confer neuroprotection.

    Evidence Co-IP, S-nitrosylation and C275S mutagenesis, E3 ligase assay, in vivo neurotoxicity model

    PMID:23027902

    Open questions at the time
    • Threshold of NO needed to switch from activation to inhibition unclear
    • Generalizability beyond NMDA neurotoxicity not established
  13. 2014 High

    Placed SIAH1 in ER-stress signaling, induced via PERK/ATF4 and IRE1/sXBP1 and amplifying ATF4-driven death, with genetic protection from ischemia in compound-knockout mice.

    Evidence Compound knockout mice, MCAO model, ATF4 hydroxylation assay, siRNA

    PMID:24809345

    Open questions at the time
    • SIAH1 versus SIAH2 individual contributions not separated
    • Direct ATF4 hydroxylase target not biochemically identified
  14. 2012 High

    Defined SIAH1 control of transcriptional elongation by degrading ELL1/ELL2, with access blocked when ELL2 is sequestered in the super elongation complex, linking SIAH1 levels to HIV-1 transcription.

    Evidence Co-IP, ubiquitination assay, siRNA, HIV transcription reporters across multiple studies

    PMID:22483617 PMID:29949759 PMID:32152128 PMID:32479599

    Open questions at the time
    • Quantitative balance between SEC-bound protection and SIAH1-driven turnover in vivo unclear
    • Multiple competing protective factors (HCF1/2, DBC1/acetylation, PARP1) not integrated into one model
  15. 2019 High

    Showed isoform-selective substrate targeting in neurons, with SIAH1 degrading Akt3 specifically to restrain axonal branching, and a disease somatic mutation escaping degradation.

    Evidence Co-IP, ubiquitination assay, knockdown, Akt3-E17K mutagenesis, primary neuron imaging

    PMID:31471318

    Open questions at the time
    • Structural basis for Akt3 versus Akt1/2 selectivity unknown
    • In vivo developmental phenotype not established
  16. 2022 High

    Expanded SIAH1's tumor-suppressive substrate set, degrading YBX-1, CPSF1, and FRK-phosphorylated YAP to influence chemosensitivity, splice-variant generation, and glioblastoma growth.

    Evidence Co-IP, site-specific ubiquitination mutagenesis, splicing/minigene and in vivo tumor assays

    PMID:35273154 PMID:35402071 PMID:35723276

    Open questions at the time
    • m6A and phospho-dependent regulation of these axes not unified
    • Relative dominance among many competing substrates in a given cell type unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SIAH1's single dimeric substrate-binding surface achieves recognition of dozens of structurally unrelated substrates, and what determines degradative versus non-degradative ubiquitination, remains unresolved.
  • No co-structure with a bound degron substrate
  • Rules governing mono/di- versus poly-ubiquitination outcomes unknown
  • Hierarchy among competing substrates and regulators in vivo not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016874 ligase activity 5 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2
Partners
BETA-CATENINELL2GAPDHHIPK2SIP/CACYBPSKP1TBL1UBCH8
Complex memberships
SIAH1 homodimerSIAH1/SIP(CacyBP)/Skp1/Ebi SCF-like ligase complex

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SIAH-1 N-terminal RING domain is required for proteolysis of target proteins (DCC), while C-terminal sequences regulate oligomerization and binding to substrates. Point mutations or deletion of the RING domain abolish DCC degradation and stabilize SIAH-1 itself. SIAH-1 undergoes self-degradation via the proteasome, blocked by RING domain mutations. Mutagenesis, co-immunoprecipitation, proteasome inhibitor assays, antisense knockdown Molecular and cellular biology High 9858595
2001 SIAH-1 forms an SCF-like E3 ubiquitin ligase complex with SIP (a Sgt1 homolog), Skp1, and the F-box protein Ebi to mediate phosphorylation-independent degradation of beta-catenin; complex assembly is induced by p53 activation, linking genotoxic injury to beta-catenin destruction and reduced TCF/LEF activity. Co-immunoprecipitation, co-expression degradation assays, yeast two-hybrid Molecular cell High 11389839 11389840
2001 SIAH-1 interacts with the C-terminus of APC and promotes GSK3beta-phosphorylation-independent, beta-TrCP-independent degradation of beta-catenin; demonstrated by beta-catenin loss in mammalian cells and hypodorsalization in Xenopus embryos. Co-immunoprecipitation, overexpression degradation assay, Xenopus embryo microinjection Molecular cell High 11389840
2001 SIAH-1 directly interacts with and promotes proteasomal degradation of Numb, leading to redistribution of Notch to the cytoplasm/nucleus and augmented Notch-regulated transcription. Co-immunoprecipitation, pulse-chase degradation assay, reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 11752454
2002 Crystal/structural analysis revealed that SIAH-1 forms a dimer with a large electronegative concave surface across the dimer interface; site-directed mutagenesis of electronegative residues abolished SIAH-1 binding to SIP both in vitro and in cells. Structure-based analysis, site-directed mutagenesis, binding assay The Journal of biological chemistry High 12421809
2003 SIAH-1 ubiquitinates and promotes proteasomal degradation of synphilin-1 via its RING finger domain; SIAH-1 interacts with the N-terminus of synphilin-1 through its substrate-binding domain; this degradation abrogates synphilin-1's inhibitory effect on dopamine release from PC12 cells. Notably, SIAH-1 does not ubiquitinate or degrade wild-type or mutant alpha-synuclein under these conditions. Yeast two-hybrid, co-immunoprecipitation from rat brain, confocal microscopy, ubiquitination assay, dopamine release assay The Journal of biological chemistry High 14506261
2003 PEG10 protein associates with SIAH1 and overexpression of PEG10 decreases SIAH1-mediated cell death, suggesting PEG10 functions as an antagonist of SIAH1 pro-apoptotic activity. Co-immunoprecipitation, cell death assay with overexpression Cancer research Low 12810624
2004 SIAH-1 binds an octapeptide sequence in T-STAR and targets it for proteasome-dependent degradation; a double amino acid substitution in mouse T-STAR that mimics the human SIAH1-binding site brings mouse T-STAR under SIAH1 control. SIAH1-mediated degradation modulates T-STAR-dependent alternative splicing. Two-hybrid screening, in vivo degradation assay, minigene splicing assay, mutagenesis Human molecular genetics High 15163637
2005 S-nitrosylation of GAPDH at Cys-150 triggers its binding to SIAH-1; SIAH-1's nuclear localization signal mediates nuclear translocation of GAPDH; nuclear GAPDH stabilizes SIAH-1, facilitating SIAH-1-mediated degradation of nuclear proteins and apoptosis. Activation of macrophages or neurons elicits GAPDH-SIAH-1 binding and nuclear translocation. Co-immunoprecipitation, S-nitrosylation assay, nuclear fractionation, cell death assays, NO deletion experiments Nature cell biology High 15951807
2005 Crystal structure of the SIAH-1–SIP complex revealed that SIP engages SIAH-1 via two elements: an N-terminal dimerization domain across the upper surface of the SIAH-1 dimer through a PXAXVXP consensus motif, and a C-terminal Skp1-binding domain protruding from the lower surface. Both elements are required for beta-catenin destruction. X-ray crystallography, NMR, mutagenesis, cell-based beta-catenin degradation assay The Journal of biological chemistry High 16085652
2005 SIAH-1 interacts with the scaffold protein POSH to activate the JNK apoptotic pathway; E3 ligase activity of SIAH-1 is required for this proapoptotic effect. Apoptotic stimuli stabilize SIAH-1 protein via a mechanism dependent on JNK pathway activation, POSH interaction, and phosphorylation of SIAH-1 at tyrosines 100 and 126. Co-immunoprecipitation, siRNA knockdown, phosphorylation mutagenesis, cell death assays The Journal of biological chemistry Medium 16230351
2006 SIAH-1 ubiquitinates and promotes proteasomal degradation of FIH (factor inhibiting HIF-1alpha) under hypoxic conditions; SIAH-1 interacts with the JmjC domain of FIH through its substrate-binding domain and uses its RING domain for ubiquitination, thereby regulating HIF-1alpha transcriptional activity. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, proteasome inhibitor experiments Biochemical and biophysical research communications Medium 17188242
2006 EBV oncoprotein LMP1 upregulates SIAH-1 protein stability, which in turn promotes proteasomal degradation of prolyl hydroxylases PHD1 and PHD3, preventing VHL-HIF-1alpha complex formation and stabilizing HIF-1alpha to activate angiogenic gene expression. Co-immunoprecipitation, siRNA knockdown, proteasome inhibitor assay, immunoblot Cancer research Medium 17047048
2007 SIAH-1 binds alpha-synuclein and UbcH8 (a brain-enriched E2 enzyme) and catalyzes mono- and di-ubiquitination of alpha-synuclein in vivo; this ubiquitination does not target alpha-synuclein for proteasomal degradation but promotes its aggregation and toxicity. The PD-linked A30P mutation disrupts this ubiquitination; A53T does not. Co-immunoprecipitation, in vivo ubiquitination assay, aggregation assay, mutagenesis Human molecular genetics High 18065497
2008 SIAH-1 colocalizes with and ubiquitinates HIPK2 in unstressed cells, targeting it for proteasomal degradation. DNA damage triggers ATM/ATR-dependent phosphorylation of SIAH-1 at Ser-19, disrupting the HIPK2-SIAH-1 complex and stabilizing HIPK2 to promote apoptosis. Conversely, after sublethal damage, p53-induced SIAH-1 expression drives HIPK2 degradation to promote recovery. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, site-directed mutagenesis of Ser-19, ATM/ATR inhibitor experiments Nature cell biology High 18536714
2008 Structure of S100A6 bound to a SIP fragment (residues 189-219) determined by NMR; SIP(189-219) forms two helices engaging S100A6 in both canonical and novel binding modes. Structure-based mutagenesis confirmed reduced binding; cell-based assay showed S100A6 modulates SCF(TBL1)/SIAH-1 complex activity on beta-catenin. NMR structure determination, isothermal titration calorimetry, mutagenesis, cell-based functional assay Biochemistry High 18803400
2008 SIAH-1 interacts with, ubiquitinates, and promotes proteasomal degradation of TRB3 (Tribbles 3 homolog); co-expression of SIAH-1 reverses TRB3-mediated upregulation of TGF-beta signaling. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, overexpression degradation assay Cellular signalling Medium 18276110
2009 SIAH-1 ubiquitinates EB3 (end-binding protein 3) promoting its proteasomal degradation; Aurora-A and Aurora-B phosphorylate EB3 at Ser-176, disrupting the EB3-SIAH-1 complex to stabilize EB3 during mitosis and facilitate cell cycle progression at prometaphase. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, phosphorylation site mutagenesis, cell cycle analysis The Journal of biological chemistry High 19696028
2009 SIAH-1 is required for high glucose-induced GAPDH nuclear accumulation and cell death in retinal Müller cells; SIAH-1 forms a complex with GAPDH under hyperglycemic conditions and is predominantly nuclear; siRNA knockdown of SIAH-1 blocks GAPDH nuclear translocation and prevents high glucose-induced cell death via inhibiting p53 phosphorylation. siRNA knockdown, co-immunoprecipitation, nuclear fractionation, cell death assay (annexin V, caspase) The Journal of biological chemistry Medium 19940145
2010 SIAH-1 alone is sufficient to polyubiquitinate beta-catenin in vitro; TBL1 competes with SIAH-1 for binding to the same armadillo repeat domain of beta-catenin, protecting beta-catenin from SIAH-1-mediated ubiquitination and proteasomal degradation during Wnt signaling. In vitro ubiquitination assay with purified components, co-immunoprecipitation, overexpression/knockdown degradation assay The Journal of biological chemistry High 20181957
2011 SIAH-1 (but not SIAH-2) is the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation; SIAH-1 cannot access ELL2 when bound in the AFF4 super elongation complex (SEC). At high concentrations, SIAH-1 also degrades AFF4/1 to dismantle SECs. Prostratin and HMBA activate HIV transcription by decreasing SIAH-1 expression and ELL2 ubiquitination. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression, HIV transcription reporter assay Molecular cell High 22483617
2011 SIAH-1 interacts with and promotes ubiquitin/proteasome-dependent degradation of the hepatitis B viral X protein (HBx), attenuating HBx-mediated transactivation of GRE, HSE, and CRE promoters; SIAH-1 participates in p53-mediated HBx degradation. Co-immunoprecipitation, ubiquitination assay, transcriptional reporter assay FEBS letters Medium 21878328
2011 SIAH-1 interacts with, polyubiquitinates, and promotes proteasomal degradation of PML-RARα via the E2 enzyme UBCH8; TRIAD1 also binds UBCH8 and PML-RARα but, in contrast to SIAH-1/SIAH-2, does not affect PML-RARα turnover. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown degradation assay The international journal of biochemistry & cell biology Medium 22037423
2011 SIAH-1 interacts with and promotes ubiquitination and proteasomal degradation of HSV ICP0; ICP0 in turn stabilizes SIAH-1 and recruits it into ICP0-containing nuclear bodies. In SIAH-1 knockdown cells, ICP0 levels are higher, less ubiquitinated, and more stable. Co-immunoprecipitation, ubiquitination assay in vitro and in vivo, siRNA knockdown, half-life assay Journal of virology Medium 21632771
2011 SIAH-1 is required for synphilin-1-dependent PINK1-independent mitophagy; synphilin-1 recruits SIAH-1 to mitochondria where SIAH-1 promotes mitochondrial protein ubiquitination and subsequent mitophagy. Catalytically inactive SIAH-1 mutant or SIAH-1 knockdown abrogates this mitophagy pathway. Co-immunoprecipitation, siRNA knockdown, dominant-negative mutant, LC3/Lamp1 recruitment assay, mitophagy flux assay (Atg5 knockdown) Human molecular genetics Medium 27334109
2012 B23/nucleophosmin binds both SIAH-1 and GAPDH in the nucleus; trans-nitrosylation of B23 at Cys-275 by GAPDH enhances B23-SIAH-1 interaction and disrupts the SIAH-1-GAPDH complex; S-nitrosylated B23 abrogates SIAH-1 E3 ligase activity, providing neuroprotection against NMDA-mediated neurotoxicity. Co-immunoprecipitation, S-nitrosylation assay, mutagenesis (C275S), E3 ligase activity assay, in vivo neurotoxicity model The Journal of cell biology High 23027902
2014 SIAH-1/2 are transcriptionally induced by ER stress through PERK/ATF4 and IRE1/sXBP1 pathways; SIAH-1/2 attenuate proline hydroxylation of ATF4, stabilizing it and amplifying ER stress-induced cell death. Siah1a+/-::Siah2-/- mice show smaller infarct volume and protection from ischemia-induced death compared to WT. Genetic mouse model (compound knockout), siRNA knockdown in cultured cells, middle cerebral artery occlusion model, ATF4 hydroxylation assay PLoS genetics High 24809345
2014 SIAH-1/SIP E3 ligase complex mediates glucose starvation-induced proteasomal degradation of cytoplasmic p27(kip1), thereby decreasing cell motility; SIP-/- fibroblasts have elevated cytoplasmic p27 and increased cell migration. siRNA knockdown, SIP knockout fibroblasts, co-immunoprecipitation, proteasome inhibitor assay, cell migration assay Cell cycle (Georgetown, Tex.) Medium 21734459
2014 ASK1 (apoptosis signal-regulating kinase 1) interacts with both GAPDH and SIAH-1 and phosphorylates SIAH-1 at Thr-70/74 and Thr-235/239; this phosphorylation triggers GAPDH-SIAH-1 stress signaling and activates p300 acetyltransferase in the nucleus. Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, p300 activation assay The Journal of biological chemistry Medium 25391652
2015 High glucose increases SIAH-1 protein levels, induces GAPDH-SIAH-1 complex formation, and causes GAPDH nuclear translocation in human retinal pericytes; blocking the GAPDH-SIAH-1 interaction with directed peptides prevents high glucose-induced pericyte apoptosis. Co-immunoprecipitation, siRNA knockdown, GAPDH/SIAH-1-blocking peptides, nuclear fractionation, apoptosis assay (annexin V, caspase-3) The Journal of biological chemistry Medium 26438826
2018 PARP1 suppresses SIAH-1 at both mRNA level (via NCoR co-repressor complex) and protein level (promoting PARylation-dependent ubiquitination of SIAH-1), thereby elevating ELL2 to form more super elongation complexes and activate HIV-1 transcription. siRNA knockdown, PARP1 inhibitor, co-immunoprecipitation, ubiquitination assay, HIV transcription assay Cell reports Medium 29949759
2019 SIAH-1 ubiquitinates Akt3 (but not Akt1 or Akt2) preferentially and promotes its degradation; Akt3 is enriched in axonal shafts where SIAH-1 is prominent. Depletion of SIAH-1 elevates Akt3 levels and causes aberrant axonal branching. The brain-specific Akt3-E17K somatic mutation escapes SIAH-1-mediated degradation, causing dysmorphic neurons. Co-immunoprecipitation, ubiquitination assay, siRNA/shRNA knockdown, overexpression with mutagenesis, primary neuron imaging The Journal of biological chemistry High 31471318
2020 HCF1 and HCF2 bind and block the substrate-binding domain (SBD) of SIAH-1/2 to prevent SIAH-1 autoubiquitination and trans-ubiquitination of ELL2, thereby stabilizing ELL2 and enhancing super elongation complex formation for HIV-1 transactivation. Co-immunoprecipitation, in vitro ubiquitination assay, HCF1/2 knockdown, HIV transcription assay Nucleic acids research Medium 32479599
2020 DBC1 competes with HDAC3 for the same binding sites on ELL1, promoting p300-mediated ELL1 acetylation which stabilizes it against SIAH-1-mediated polyubiquitylation; SIAH-1 ubiquitylates deacetylated ELL1 for proteasomal degradation. Co-immunoprecipitation, ubiquitination assay, acetylation assay, siRNA knockdown, competition binding assay Proceedings of the National Academy of Sciences of the United States of America Medium 32152128
2020 SIAH-1 binds to and ubiquitinates MyD88, targeting it for proteasomal degradation; SIAH-1 knockdown increases MyD88-dependent TLR7 signaling; dengue virus induces SIAH-1 expression via the unfolded protein response during infection, dampening innate immunity. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, CRISPR MyD88 knockout, TLR7 signaling assay Frontiers in microbiology Medium 32117091
2022 SIAH-1 ubiquitinates YBX-1 at Lys304 via its RING finger domain in the cytoplasm, targeting it for degradation; YBX-1 destabilization leads to instability of its m5C-modified mRNA targets, sensitizing ovarian cancer cells to cisplatin. Co-immunoprecipitation, ubiquitination assay with site-specific mutagenesis (Lys304), siRNA knockdown, in vitro and in vivo tumor assays Oncogenesis High 35273154
2022 SIAH-1 ubiquitinates XIAP, targeting it for proteasomal degradation in nucleus pulposus cells; this promotes NPC senescence and apoptosis in intervertebral disc degeneration; METTL3-mediated m6A methylation of SIAH-1 mRNA enhances its expression. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, m6A RIP, actinomycin D mRNA stability assay Tissue & cell Medium 35580525
2022 FRK phosphorylates YAP at Tyr391/407/444, which recruits SIAH-1 to catalyze YAP ubiquitination and proteasomal degradation in glioblastoma; SIAH-1 is required for YAP destabilization initiated by FRK. Co-immunoprecipitation, proximity ligation assay, ubiquitination assay, phosphorylation site mutagenesis, siRNA knockdown, in vivo tumor model Neuro-oncology High 35723276
2000 SIAH-1 interacts with alpha-tubulin and promotes proteasomal degradation of the chromokinesin Kid (KIF22) via its RING finger domain during mitosis; overexpression of SIAH-1 but not a deletion mutant lacking the N-terminal domain reduces kinesin levels and disrupts mitosis. Yeast two-hybrid, co-immunoprecipitation, overexpression degradation assay, dominant-negative mutant Oncogene Medium 11146551
2001 SIAH-1 interacts via its C-terminal part with the N-terminus of OBF-1 transcriptional coactivator, leading to OBF-1 protein downregulation via the ubiquitin-proteasome pathway without changing OBF-1 mRNA, and reducing octamer site-dependent transcription; inhibiting the proteasome in B cells elevates OBF-1 protein. Yeast two-hybrid, co-immunoprecipitation, proteasome inhibitor assay, reporter gene assay, domain mutagenesis The EMBO journal Medium 11483517
2003 SIAH-1 interacts with CtIP (CtBP-interacting protein) and promotes its proteasomal degradation; however, p21(WAF1) induction by SIAH-1 does not require CtIP degradation, as a RING-deleted SIAH-1 that binds but cannot degrade CtIP still induces p21 transcription to a similar extent. Yeast two-hybrid, co-immunoprecipitation, ubiquitin-proteasome assay, reporter assay, dominant-negative mutant Oncogene Medium 14654780
2004 SIAH-1 interacts with the cytoplasmic C-terminus of polycystin-1 (PKD1) and promotes its ubiquitination and proteasomal degradation, shortening PKD1-C half-life; overexpression of SIAH-1 promotes degradation of polycystin-1 in membrane-anchored chimeric proteins. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, pulse-chase half-life assay Journal of the American Society of Nephrology Medium 15284290
2007 KSHV ORF45 protein interacts with SIAH-1, and SIAH-1 promotes proteasomal degradation of ORF45 through a RING domain-dependent mechanism in infected cells. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, half-life assay Journal of virology Medium 18077711
2009 SIAH-1 mediates proteasomal degradation of HIPK2; this degradation is blocked by MLK3, EBV LMP-1, or DNA damaging stimuli, revealing multiple pathways that stabilize HIPK2 by escaping SIAH-1-dependent degradation. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, overexpression/knockdown Cancer letters Medium 19250734
2011 EHMT2 histone methyltransferase suppresses SIAH1 transcription by binding its promoter region (-293 to +51) and methylating H3K9, thereby reducing SIAH1 expression and promoting cancer cell proliferation. ChIP, promoter reporter assay, siRNA knockdown, western blot Neoplasia (New York, N.Y.) Medium 21847359
2011 SIAH-1 ubiquitinates and promotes proteasomal degradation of synaptophysin under combined hypoxia and high glucose conditions, mediated by ERK pathway activation; ERK inhibition or SIAH-1 knockdown rescues synaptophysin levels. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, overexpression, ERK inhibitor American journal of translational research Medium 25755825
2017 SIAH-1/2 promote Th17 cell differentiation by maintaining stability of HIF-1alpha protein, which directly regulates Il17a and Rorgt transcription; in the absence of HIF-1alpha, SIAH1 and SIAH2 have little effect on Th17 differentiation. cDNA library screen, promoter reporter assay, ex vivo Th17 differentiation, genetic (HIF-1alpha knockout) epistasis International immunology Medium 28338984
2017 HIF-1alpha occupies the SIAH1 promoter in response to nutritional stress and recruits the histone demethylase KDM3A (via p300 crosstalk) to activate SIAH1 transcription through H3K9 demethylation and H3K4 trimethylation/H3 acetylation; HIF-1alpha or KDM3A depletion prevents SIAH1 induction. ChIP, siRNA knockdown, chetomin inhibitor, promoter reporter assay, histone modification analysis Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28843785
2019 SIAH-1 ubiquitinates ZEB1, targeting it for proteasomal degradation; SIAH-1 overexpression inhibits ZEB1 expression and sensitizes drug-resistant osteosarcoma cells to doxorubicin; upregulation of ZEB1 in resistant cells is due to increased protein half-life associated with reduced SIAH-1 activity. siRNA/overexpression, proteasome inhibitor, western blot half-life analysis Biological chemistry Low 30265649
2022 SIAH-1 directly interacts with and promotes ubiquitination/degradation of CPSF1; CPSF1 degradation by SIAH-1 reduces generation of the oncogenic AR-v7 splice variant by removing CPSF1 binding to the AR-cryptic exon CE3 polyadenylation signal; m6A methylation of SIAH1 mRNA in PCa represses its expression. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, m6A analysis, minigene/splicing assay Molecular therapy. Nucleic acids Medium 35402071
2009 E2F1 transcription factor directly binds two putative E2F1-binding sites upstream of the SIAH1 transcription start site, activates SIAH1 promoter activity (by luciferase assay and ChIP), and elevates SIAH1 protein levels, thereby suppressing beta-catenin/TCF activity. Chromatin immunoprecipitation, luciferase reporter assay, shRNA knockdown, western blot Journal of cellular and molecular medicine Medium 20187294
2002 SIAH-1 promoter has no TATA or CCAAT box; an Sp1 site is responsible for basal promoter activity; p53 upregulates SIAH-1 mRNA but does not directly activate the proximal promoter in reporter assays, suggesting the p53 responsive element lies in a different region. Promoter deletion/mutation reporter assay, Northern blot, co-transfection FEBS letters Medium 11852084
2007 A novel splice variant of SIAH-1, designated Siah-1S, forms heterodimers with SIAH-1 or homodimers that cannot bind SIP; Siah-1S catalyzes self-ubiquitination and acts as a dominant-negative against SIAH-1 to upregulate beta-catenin/TCF activity and antagonize SIAH-1-mediated apoptosis. Co-immunoprecipitation, dimerization assay, ubiquitination assay, reporter assay, soft agar colony assay Oncogene Medium 17420721
2022 SIAH-1 is essential for sorafenib-induced mitophagy; SIAH-1 silencing markedly represses mitophagy and sensitizes cells to sorafenib-induced death in hepatocellular carcinoma cells. siRNA knockdown, mitophagy flux assay (mKeima-Red, LC3, PINK1 accumulation), combination treatment in vitro and in vivo Experimental & molecular medicine Medium 36385558

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nature cell biology 886 15951807
2001 Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Molecular cell 523 11389839
2001 Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Molecular cell 367 11389840
2002 Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proceedings of the National Academy of Sciences of the United States of America 227 12399545
1999 Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins. Molecular and cellular biology 215 9858595
2008 Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nature cell biology 167 18536714
2016 The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway. Human molecular genetics 146 27334109
2007 Ubiquitination of alpha-synuclein by Siah-1 promotes alpha-synuclein aggregation and apoptotic cell death. Human molecular genetics 145 18065497
2003 Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer research 143 12810624
2006 EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells. Cancer research 118 17047048
1999 SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: identification of common effectors with p53 and p21(Waf1). Proceedings of the National Academy of Sciences of the United States of America 104 10393949
2011 Enhanced expression of EHMT2 is involved in the proliferation of cancer cells through negative regulation of SIAH1. Neoplasia (New York, N.Y.) 101 21847359
2003 Siah-1 facilitates ubiquitination and degradation of synphilin-1. The Journal of biological chemistry 94 14506261
2017 LncRNA SNHG1 promotes α-synuclein aggregation and toxicity by targeting miR-15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells. Neurotoxicology 91 29217406
2010 Direct ubiquitination of beta-catenin by Siah-1 and regulation by the exchange factor TBL1. The Journal of biological chemistry 88 20181957
2005 Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex. The Journal of biological chemistry 87 16085652
2001 Siah-1 binds and regulates the function of Numb. Proceedings of the National Academy of Sciences of the United States of America 82 11752454
2000 SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis. Oncogene 75 11146551
2001 The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1. The EMBO journal 69 11483517
2012 The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription. Molecular cell 57 22483617
2005 Siah1 interacts with the scaffold protein POSH to promote JNK activation and apoptosis. The Journal of biological chemistry 56 16230351
2008 Structure of the S100A6 complex with a fragment from the C-terminal domain of Siah-1 interacting protein: a novel mode for S100 protein target recognition. Biochemistry 55 18803400
2014 miR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway. Carcinogenesis 52 24503442
2022 SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1. Oncogenesis 49 35273154
2009 Mitotic regulation of the stability of microtubule plus-end tracking protein EB3 by ubiquitin ligase SIAH-1 and Aurora mitotic kinases. The Journal of biological chemistry 48 19696028
2009 siah-1 Protein is necessary for high glucose-induced glyceraldehyde-3-phosphate dehydrogenase nuclear accumulation and cell death in Muller cells. The Journal of biological chemistry 48 19940145
2007 SIAH1 causes growth arrest and apoptosis in hepatoma cells through beta-catenin degradation-dependent and -independent mechanisms. Oncology reports 45 17273732
2011 E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein. FEBS letters 44 21878328
2004 SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. Human molecular genetics 44 15163637
2010 S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function. Amino acids 43 20182755
2018 PHF19 promotes the proliferation, migration, and chemosensitivity of glioblastoma to doxorubicin through modulation of the SIAH1/β-catenin axis. Cell death & disease 42 30323224
2016 Up-regulation of Siah1 by ethanol triggers apoptosis in neural crest cells through p38 MAPK-mediated activation of p53 signaling pathway. Archives of toxicology 41 27270636
2011 Nuclear expression of the ubiquitin ligase seven in absentia homolog (SIAH)-1 induces proliferation and migration of liver cancer cells. Journal of hepatology 41 21356256
2003 SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas. Genes, chromosomes & cancer 41 12557228
1999 SIAH-1 inhibits cell growth by altering the mitotic process. Oncogene 41 10597311
2019 The SIAH1-HIPK2-p53ser46 Damage Response Pathway is Involved in Temozolomide-Induced Glioblastoma Cell Death. Molecular cancer research : MCR 40 30796178
2002 Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP). The Journal of biological chemistry 40 12421809
2016 Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells. BMC cancer 39 27377268
2012 S-nitrosylation of B23/nucleophosmin by GAPDH protects cells from the SIAH1-GAPDH death cascade. The Journal of cell biology 39 23027902
2008 E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3. Cellular signalling 38 18276110
2004 Inactivating mutations of the Siah-1 gene in gastric cancer. Oncogene 37 15467739
2003 SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene 37 14654780
2018 The PARP1-Siah1 Axis Controls HIV-1 Transcription and Expression of Siah1 Substrates. Cell reports 35 29949759
2014 Fine tuning of the UPR by the ubiquitin ligases Siah1/2. PLoS genetics 34 24809345
2011 Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic stress. Cell cycle (Georgetown, Tex.) 33 21734459
2008 Abundance of aspargynyl-hydroxylase FIH is regulated by Siah-1 under normoxic conditions. Neuroscience letters 33 18280659
2022 Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy. Experimental & molecular medicine 32 36385558
2012 Calcyclin binding protein and Siah-1 interacting protein in Alzheimer's disease pathology: neuronal localization and possible function. Neurobiology of aging 32 23260124
2004 Siah-1 interacts with the intracellular region of polycystin-1 and affects its stability via the ubiquitin-proteasome pathway. Journal of the American Society of Nephrology : JASN 31 15284290
2015 High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1. The Journal of biological chemistry 29 26438826
2010 The expression of SIAH1 is downregulated and associated with Bim and apoptosis in human breast cancer tissues and cells. Molecular carcinogenesis 29 20082325
2009 Stabilization of HIPK2 by escape from proteasomal degradation mediated by the E3 ubiquitin ligase Siah1. Cancer letters 28 19250734
2017 HIF-1α coordinates epigenetic activation of SIAH1 in hepatocytes in response to nutritional stress. Biochimica et biophysica acta. Gene regulatory mechanisms 27 28843785
2015 MiR-107 down-regulates SIAH1 expression in human breast cancer cells and silencing of miR-107 inhibits tumor growth in a nude mouse model of triple-negative breast cancer. Molecular carcinogenesis 27 25851994
2011 Herpes simplex virus immediate-early protein ICP0 is targeted by SIAH-1 for proteasomal degradation. Journal of virology 26 21632771
2009 SIAH1 induced apoptosis by activation of the JNK pathway and inhibited invasion by inactivation of the ERK pathway in breast cancer cells. Cancer science 26 19775288
2006 Siah-1 facilitates ubiquitination and degradation of factor inhibiting HIF-1alpha (FIH). Biochemical and biophysical research communications 26 17188242
2011 Differential regulation of PML-RARα stability by the ubiquitin ligases SIAH1/SIAH2 and TRIAD1. The international journal of biochemistry & cell biology 24 22037423
2022 Reactive oxygen species-induced SIAH1 promotes granulosa cells' senescence in premature ovarian failure. Journal of cellular and molecular medicine 23 35261172
2014 Ubiquitin ligase Siah1 promotes the migration and invasion of human glioma cells by regulating HIF-1α signaling under hypoxia. Oncology reports 23 25572001
2007 SIAH-1 interacts with the Kaposi's sarcoma-associated herpesvirus-encoded ORF45 protein and promotes its ubiquitylation and proteasomal degradation. Journal of virology 23 18077711
2020 Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation. Cancer cell international 22 32082080
2020 The E3 Ubiquitin Ligase SIAH1 Targets MyD88 for Proteasomal Degradation During Dengue Virus Infection. Frontiers in microbiology 22 32117091
2014 The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells. Cellular signalling 22 24882689
2009 E2F1 represses beta-catenin/TCF activity by direct up-regulation of Siah1. Journal of cellular and molecular medicine 22 20187294
2000 Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene. International journal of cancer 21 10956387
2020 DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes. Proceedings of the National Academy of Sciences of the United States of America 20 32152128
2019 Identification and characterization of small molecule inhibitors of the ubiquitin ligases Siah1/2 in melanoma and prostate cancer cells. Cancer letters 20 30771432
2017 Membrane-bound β-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells. Oncogenesis 20 28481365
2017 Hepatitis B virus X protein activates E3 ubiquitin ligase Siah-1 to control virus propagation via a negative feedback loop. The Journal of general virology 20 28714848
2010 Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in normal tissues and in the breast tumoral processes. Journal of experimental & clinical cancer research : CR 20 20144232
2017 CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27. Cell biology international 19 29024247
2009 Isoreserpine promotes beta-catenin degradation via Siah-1 up-regulation in HCT116 colon cancer cells. Biochemical and biophysical research communications 19 19607803
2019 SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development. The Journal of biological chemistry 18 31471318
2014 Role of apoptosis signal-regulating kinase 1 (ASK1) as an activator of the GAPDH-Siah1 stress-signaling cascade. The Journal of biological chemistry 18 25391652
2020 Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2. Nucleic acids research 17 32479599
2016 E3 Ubiquitin Ligase Siah-1 is Down-regulated and Fails to Target Natural HBx Truncates for Degradation in Hepatocellular Carcinoma. Journal of Cancer 17 26918055
2015 E3 ubiquitin ligase Siah-1 downregulates synaptophysin expression under high glucose and hypoxia. American journal of translational research 17 25755825
2020 MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway. Frontiers in cell and developmental biology 16 33134300
2018 PUM1 and PUM2 exhibit different modes of regulation for SIAH1 that involve cooperativity with NANOS paralogues. Cellular and molecular life sciences : CMLS 16 30269240
2017 E3 ubiquitin ligases SIAH1/2 regulate hypoxia-inducible factor-1 (HIF-1)-mediated Th17 cell differentiation. International immunology 16 28338984
2014 Sec6 regulated cytoplasmic translocation and degradation of p27 via interactions with Jab1 and Siah1. Cellular signalling 16 24949832
2007 Siah-1S, a novel splice variant of Siah-1 (seven in absentia homolog), counteracts Siah-1-mediated downregulation of beta-catenin. Oncogene 16 17420721
2022 Circ-CCNB1 Modulates Trophoblast Proliferation and Invasion in Spontaneous Abortion by Regulating miR-223/SIAH1 axis. Endocrinology 15 35731831
2019 SIAH1/ZEB1/IL-6 axis is involved in doxorubicin (Dox) resistance of osteosarcoma cells. Biological chemistry 15 30265649
2018 Tp53 Mutation Inhibits Ubiquitination and Degradation of WISP1 via Down-Regulation of Siah1 in Pancreatic Carcinogenesis. Frontiers in pharmacology 15 30123132
2011 Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1. Molecular and cellular biochemistry 15 21633900
2010 Siah1 proteins enhance radiosensitivity of human breast cancer cells. BMC cancer 15 20682032
2022 m6A-induced repression of SIAH1 facilitates alternative splicing of androgen receptor variant 7 by regulating CPSF1. Molecular therapy. Nucleic acids 14 35402071
2022 SIAH1 promotes senescence and apoptosis of nucleus pulposus cells to exacerbate disc degeneration through ubiquitinating XIAP. Tissue & cell 14 35580525
2022 FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1. Neuro-oncology 14 35723276
2018 The E3 Ubiquitin Ligase Siah-1 Suppresses Avian Reovirus Infection by Targeting p10 for Degradation. Journal of virology 14 29321312
2016 Jab1 promotes glioma cell proliferation by regulating Siah1/β-catenin pathway. Journal of neuro-oncology 14 27640199
2022 Siah1 promotes the proliferation of NSCLC cells through ubiquitinating and stabilizing Notch1. Experimental cell research 13 35961388
2020 TRAF4, a new substrate of SIAH1, participates in chemotherapy resistance of breast cancer cell by counteracting SIAH1-mediated downregulation of β-catenin. Breast cancer research and treatment 13 32671611
2018 Knockdown of miR-299-5p inhibits the progression of hepatocellular carcinoma by targeting SIAH1. Bulletin du cancer 13 30266288
2023 SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis. Cancer cell international 12 37062828
2002 The characterization of the human Siah-1 promoter(1). FEBS letters 12 11852084
2021 miR-129-5p Ameliorates Ischemic Brain Injury by Binding to SIAH1 and Activating the mTOR Signaling Pathway. Journal of molecular neuroscience : MN 11 34355355
2006 Mutation analysis of the seven in absentia homolog 1 (SIAH1) gene in Parkinson's disease. Journal of neural transmission (Vienna, Austria : 1996) 11 16752048

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