Affinage

SMG1

Serine/threonine-protein kinase SMG1 · UniProt Q96Q15

Length
3661 aa
Mass
410.5 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 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

SMG1 is a PI3K-related serine/threonine protein kinase that serves as the central initiating kinase of nonsense-mediated mRNA decay (NMD), an mRNA surveillance pathway that degrades transcripts bearing premature termination codons (PMID:11331269, PMID:20566848). It exhibits intrinsic kinase activity, autophosphorylating and directly phosphorylating the NMD effector UPF1 at SQ motifs—activity that is abolished by active-site mutation (PMID:11331269); cryo-EM of a substrate-bound active site explains the specificity for SQ motifs requiring a glutamine at +1 and a hydrophobic residue at -1 (PMID:32469312). This function is deeply conserved, present from plants to mammals and traceable to the last common eukaryotic ancestor, and in mice SMG1 is essential for embryogenesis and governs the transcriptome through NMD-coupled clearance of PTC-containing splice variants (PMID:20566848, PMID:24103012). SMG1 operates within the SMG1-SMG8-SMG9 (SMG1C) complex, whose kinase activity is held in check by two layers of autoinhibition—the SMG8 C-terminal kinase inhibitory domain capping the catalytic pocket, relieved by SMG9 GTP hydrolysis, and the SMG1 insertion domain that blocks substrate access—and is potentiated by an InsP6 cofactor bound at a site shared with mTOR (PMID:31792449, PMID:31729466, PMID:34698635). Substrate handoff is organized by recruitment of UPF1 and UPF2 to sites near the kinase domain, with UPF2 engaging the SMG1 FRB domain, and by the RNA helicase DHX34, which scaffolds SMG1-mediated UPF1 phosphorylation through a C-terminal domain that binds SMG1 (PMID:25002321, PMID:26841701). SMG1 stability itself is maintained by CK2-phosphorylated TEL2 recruiting the R2TP chaperone complex, coupling chaperone availability to NMD efficiency (PMID:20864032, PMID:23831331). Beyond NMD, SMG1 phosphorylates p53 on Ser15 in response to DNA double-strand breaks independently of UPF1/UPF2, participates in Staufen1-mediated mRNA decay and adipogenesis, and sustains c-FLIP levels to suppress caspase-8-dependent apoptosis (PMID:21701263, PMID:24185201, PMID:21490678).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Established that human SMG1 is a bona fide PIKK with intrinsic kinase activity that directly phosphorylates UPF1, defining the molecular activity at the heart of NMD initiation.

    Evidence Immunopurified FLAG-SMG1 in vitro kinase assays with active-site mutagenesis and direct phosphorylation of purified hUpf1

    PMID:11331269

    Open questions at the time
    • Did not resolve how SMG1 is recruited to terminating ribosomes
    • No structural basis for substrate selectivity at this stage
  2. 2004 High

    Genetic null analysis in C. elegans confirmed SMG-1 is required in vivo for NMD and UPF1 phosphorylation and that SMG-1 forms a complex with its substrate.

    Evidence Genetic null alleles, in vitro kinase assay, and co-IP of SMG-1 with SMG-2 (UPF1) in worm extracts

    PMID:15314158

    Open questions at the time
    • Complex composition beyond SMG-1/SMG-2 not defined
    • Mechanism of substrate activation unresolved
  3. 2010 High

    Demonstrated the physiological scope of SMG1 in mammals—essential for embryogenesis and required genome-wide for clearing PTC-containing splice variants.

    Evidence Gene-trap knockout mouse with embryonic lethality and RNA-seq of Smg1-deficient embryos

    PMID:20566848

    Open questions at the time
    • Did not separate NMD-dependent from NMD-independent contributions to lethality
    • Tissue-specific roles not addressed
  4. 2010 High

    Identified the chaperone basis of SMG1 stability, showing CK2-phosphorylated TEL2 recruits R2TP to maintain SMG1 (and other PIKK) levels.

    Evidence In vitro PIH1D1–phospho-TEL2 binding, CK2 phosphosite mutagenesis, and PIKK stability western blots

    PMID:20864032

    Open questions at the time
    • Did not establish whether R2TP also assists SMG1 folding versus only stability
    • Quantitative contribution to steady-state SMG1 not measured
  5. 2013 Medium

    Linked TEL2/CK2-driven SMG1 stability directly to NMD output and UPF1 phosphorylation, integrating chaperone control with pathway efficiency.

    Evidence CK2 inhibition, TEL2 knockdown, SMG1 stability and UPF1 phosphorylation assays, NMD reporter, co-IP

    PMID:23831331

    Open questions at the time
    • Single-lab correlation between SMG1 levels and NMD flux
    • Whether other PIKK-dependent processes are co-regulated not tested
  6. 2014 High

    Resolved how the SMG1C complex recruits and hands off NMD factors, showing UPF2 binds the SMG1 FRB domain and is transferred to UPF1 to drive its activation.

    Evidence EM of SMG1C with in vitro/in vivo interaction, competition, and mutagenesis analyses

    PMID:25002321

    Open questions at the time
    • Conformational changes inferred at low resolution
    • Kinetics of UPF2 transfer not defined
  7. 2016 High

    Identified DHX34 as a scaffold bridging UPF1 and SMG1 to enable efficient UPF1 phosphorylation, separating the helicase's binding from catalytic stimulation.

    Evidence EM of the SMG1-DHX34 complex with CTD truncation, co-IP, UPF1 phosphorylation and NMD reporter assays

    PMID:26841701

    Open questions at the time
    • Whether DHX34 acts catalytically or purely as a scaffold not fully resolved
    • Stoichiometry within the active complex unknown
  8. 2019 High

    High-resolution cryo-EM revealed the autoinhibitory architecture of SMG1C: SMG8's KID caps the active site and SMG9 GTP hydrolysis is predicted to relieve inhibition, plus an InsP6 cofactor required for optimal kinase activity.

    Evidence Cryo-EM of SMG1 and SMG1-8-9 (3.4–3.6 Å), mass spectrometry identification of InsP6, in vitro kinase assays

    PMID:31729466 PMID:31792449

    Open questions at the time
    • Direct demonstration of GTP-hydrolysis-triggered KID displacement during catalysis
    • Source and turnover of bound InsP6 in cells
  9. 2020 High

    A substrate-bound cryo-EM structure provided the first view of a human PIKK active site engaging substrate, explaining SQ-motif recognition.

    Evidence Cryo-EM of SMG1-8-9 with a UPF1 SQ-motif peptide (2.9 Å) and phosphorylation assays with substrate variants

    PMID:32469312

    Open questions at the time
    • Full-length UPF1 engagement not captured
    • How processive multi-site phosphorylation occurs not addressed
  10. 2021 High

    Defined a second autoinhibitory layer—the SMG1 insertion domain blocking substrate access, stabilized by SMG8—and the structural basis for SMG1-selective inhibition over other PIKKs.

    Evidence Cryo-EM of SMG1-9 and SMG1-8-9 with a SMG1 inhibitor or non-hydrolyzable ATP analog (2.8–3.6 Å) plus kinase assays

    PMID:34698635

    Open questions at the time
    • How insertion-domain autoinhibition is relieved in vivo not defined
    • Interplay between the two autoinhibitory mechanisms during the catalytic cycle unclear
  11. 2011 Medium

    Showed SMG1 has an NMD-independent role in genome surveillance, activating p53 on Ser15 specifically in response to DNA double-strand breaks rather than RNA damage.

    Evidence siRNA knockdown of SMG1/UPF1/UPF2/ATM, I-PpoI-induced DSBs, mRNA oxidation transfection, p53 Ser15 phosphorylation

    PMID:21701263

    Open questions at the time
    • Direct SMG1 phosphorylation of p53 not biochemically demonstrated
    • Relationship to ATM signaling not fully resolved
  12. 2011 Medium

    Identified SMG1 as a survival kinase that maintains c-FLIP to suppress caspase-8 activation and confer resistance to Smac-mimetic-induced apoptosis.

    Evidence Kinomic siRNA screen with SMG1 knockdown, caspase-8 activity, c-FLIP western blot, JNK activation assays

    PMID:21490678

    Open questions at the time
    • Whether SMG1 kinase activity directly controls c-FLIP/JNK not established
    • Substrate(s) in this pathway unknown
  13. 2012 High

    Revealed an NMD-independent tumor-suppressive and anti-inflammatory function, as Smg1 haploinsufficiency caused cancer predisposition and chronic inflammation without NMD deficiency.

    Evidence Gene-trap Smg1 heterozygous mice with cytokine measurement, NMD assays, and cancer incidence monitoring

    PMID:23277562

    Open questions at the time
    • Molecular targets underlying inflammation/oxidative damage not identified
    • Mechanistic link to the DSB/p53 role not tested
  14. 2013 Medium

    Extended SMG1 function to Staufen1-mediated mRNA decay and adipogenesis, showing kinase-dependent UPF1 phosphorylation is needed for SMD and P-body dynamics.

    Evidence Co-IP with Stau1/UPF1/Dcp1a, kinase-dead mutant, SMD reporter, P-body colocalization imaging, adipogenesis assays

    PMID:24185201

    Open questions at the time
    • Mechanistic distinction between SMD and canonical NMD substrate engagement unclear
    • Single-lab observation of adipogenesis role
  15. 2013 Medium

    Identified miR-125a/b as direct negative regulators of SMG1 that tune NMD output via the SMG1 3'UTR.

    Evidence miR-125 overexpression/knockdown, luciferase 3'UTR reporter, SMG1 protein/mRNA quantification, NMD reporter

    PMID:23583196

    Open questions at the time
    • Physiological contexts where miR-125 controls NMD not defined
    • Single-lab reporter-based evidence
  16. 2018 Medium

    Plant knockout uncovered additional SMG1 roles in DNA repair and the unfolded protein response, reinforcing functions beyond mRNA quality control.

    Evidence SMG1 knockout in Physcomitrella patens with RNA-seq, DNA damage sensitivity, and UPR tolerance assays

    PMID:29596649

    Open questions at the time
    • Mechanism connecting SMG1 to UPR not defined
    • Conservation of these roles in mammals not established here
  17. 2022 Medium

    Connected SMG1 to tumor immune evasion, showing IL-6/STAT3-induced SMG1 limits frameshift neoantigen mRNAs through NMD.

    Evidence In vivo NMD luciferase reporter, cytokine screening, murine tumor and immunotherapy models

    PMID:36443756

    Open questions at the time
    • Direct STAT3 regulation of the SMG1 locus not dissected
    • Single-lab model-dependent findings
  18. 2022 Medium

    CRISPR screening placed SMG1 in a DNA damage signaling axis, showing SMG8/9 loss confers ATR-inhibitor resistance through SMG1-mediated control of transcription/replication conflicts.

    Evidence Genome-wide CRISPR-Cas9 positive-selection screen with ATRi treatment and DNA damage response marker analysis

    PMID:36273494

    Open questions at the time
    • Direct SMG1 substrates in the ATRi response not identified
    • Relationship to canonical NMD activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SMG1's distinct NMD-dependent and NMD-independent functions (p53/DSB signaling, apoptosis resistance, inflammation, tumor immunity) are coordinated by a single kinase, and what non-UPF1 substrates mediate them, remains unresolved.
  • No direct kinase-substrate evidence for SMG1 acting on p53, c-FLIP/JNK, or α-synuclein
  • Mechanism distinguishing substrate choice between contexts unknown
  • In vivo regulation of autoinhibition relief not directly observed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0016740 transferase activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 2 R-HSA-5357801 Programmed Cell Death 1
Partners
DHX34SMG8SMG9STAU1TEL2UPF1UPF2
Complex memberships
SMG1C (SMG1-SMG8-SMG9)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Human SMG1 (hSMG-1) is a PI3K-related kinase that exhibits intrinsic protein kinase activity, including autophosphorylation and phosphorylation of the generic PIKK substrate PHAS-1. Mutation of conserved residues within the kinase domain abolishes both autophosphorylation and substrate phosphorylation. hSMG-1 directly phosphorylates hUpf1 at sites that are also phosphorylated in whole cells, establishing hSMG-1 as the human ortholog of C. elegans SMG-1 functioning in NMD. Immunopurification of FLAG-tagged hSMG1, in vitro kinase assay, autophosphorylation assay, active-site mutagenesis, phosphorylation of purified hUpf1 The Journal of biological chemistry High 11331269
2004 C. elegans SMG-1 encodes a PI3K-superfamily protein kinase required for NMD in vivo. Null alleles of smg-1 abolish NMD and SMG-2 (UPF1 ortholog) phosphorylation in vitro. SMG-1 and SMG-2 co-immunoprecipitate from crude extracts, and this interaction is maintained in smg-3 and smg-4 mutants, demonstrating direct complex formation. SMG-2 cytoplasmic localization is unaltered in smg-1 mutants. Genetic null alleles, in vitro kinase assay, co-immunoprecipitation, NMD reporter assay, subcellular localization imaging Molecular and cellular biology High 15314158
2010 Mouse Smg1 is essential for embryogenesis; homozygous knockout is lethal at embryonic day 8.5. Smg1 deficiency leads to pronounced accumulation of premature termination codon (PTC)-containing splice variant transcripts from ~9% of genes predicted to undergo AS-coupled NMD, linking SMG1 kinase activity to regulation of the mammalian transcriptome via NMD. Gene-trap knockout mouse model, RNA-seq of Smg1-deficient embryos, phenotypic analysis Proceedings of the National Academy of Sciences of the United States of America High 20566848
2010 TEL2 is constitutively phosphorylated on serines 487/491 by CK2, and this phospho-TEL2 binds the PIH1D1 subunit of the R2TP/prefoldin-like chaperone complex. Failure of TEL2 to interact with R2TP (via CK2 phosphosite mutation) results in instability of the PIKKs, principally mTOR and SMG1, establishing that the R2TP complex is required for SMG1 stability. Proteomic analyses, in vitro binding assay (PIH1D1 binds phospho-TEL2), CK2 phosphosite mutagenesis, co-immunoprecipitation, western blot for PIKK stability Molecular cell High 20864032
2013 SMG1 is not animal-specific; it is conserved across eukaryotes including plants. Homologous recombination knockout of SMG1 in the moss Physcomitrella patens reveals that SMG1 has a conserved role in the NMD pathway, establishing it as an ancient NMD effector present in the last common eukaryotic ancestor. Phylogenetic analysis, homologous recombination knockout in Physcomitrella patens, NMD reporter assay The Plant journal : for cell and molecular biology Medium 24103012
2014 SMG1C (a complex of SMG1, SMG8, and SMG9) recruits UPF1 and UPF2 to distinct sites near the kinase domain. UPF2 binds SMG1 independently of UPF1 in vivo, recognizing the FRB domain of SMG1. UPF2 can be transferred to UPF1 within SMG1C, inducing conformational changes required to activate UPF1 within an SMG1C-UPF1-UPF2 complex. Electron microscopy, in vitro and in vivo interaction analyses, competition experiments, mutagenesis, co-immunoprecipitation Structure (London, England : 1993) High 25002321
2016 The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. DHX34 has two structural units: a core that binds UPF1 and a C-terminal domain (CTD) that binds SMG1. Truncation of the DHX34 CTD compromises DHX34 binding to SMG1, impairs UPF1 phosphorylation, and abrogates NMD, without affecting UPF1 binding. Electron microscopy of SMG1-DHX34 complex, truncation analysis, co-immunoprecipitation, UPF1 phosphorylation assay, NMD reporter assay Nature communications High 26841701
2019 Cryo-EM structure of human SMG1-SMG8-SMG9 at 3.45 Å reveals the presence of inositol hexaphosphate (InsP6) bound to SMG1. The InsP6-binding site is conserved in mTOR and potentially other PIKKs, and is required for optimal in vitro phosphorylation of both SMG1 and mTOR substrates. Cryo-EM, mass spectrometry (InsP6 identification), in vitro kinase assay Nature structural & molecular biology High 31792449
2019 Cryo-EM structures of human SMG1 alone (3.6 Å) and the SMG1-SMG8-SMG9 complex (3.4 Å) reveal that SMG8 has a C-terminal kinase inhibitory domain (KID) that covers the catalytic pocket and inhibits SMG1 kinase activity. GTP hydrolysis of SMG9 is predicted to cause conformational change of SMG8-SMG9, moving the KID away from the active site to restore kinase activity. Cryo-EM structure determination, biochemical kinase activity assays Cell research High 31729466
2020 Cryo-EM structure of human SMG1-8-9 bound to a UPF1 phosphorylation site (SQ motif) at 2.9 Å provides the first snapshot of a human PIKK with a substrate-bound active site. Together with biochemical assays, this structure explains how SMG1 specifically recognizes SQ motifs with a glutamine at +1 and a hydrophobic residue at -1. Cryo-EM structure determination, biochemical phosphorylation assays with substrate variants eLife High 32469312
2021 Cryo-EM structures of SMG1-9 and SMG1-8-9 bound to a SMG1-specific inhibitor or non-hydrolyzable ATP analog (2.8–3.6 Å) reveal: (1) the molecular basis for selective inhibition of SMG1 over other PIKKs; (2) the SMG1 insertion domain can exert an autoinhibitory function by directly blocking the substrate-binding path and access to the active site; (3) SMG8 stabilizes this autoinhibitory conformation. Cryo-EM structure determination, biochemical kinase activity assays, comparison with substrate-bound structure eLife High 34698635
2012 Smg1 haploinsufficiency in mice leads to predisposition to cancer (particularly lung and hematopoietic malignancies) and chronic inflammation, with elevated basal tissue and serum cytokine levels and evidence of oxidative damage, without deficiencies in NMD. Smg1 homozygous KO mice are early embryonic lethal. Genetrap Smg1 mouse model, cytokine measurement, NMD assay, cancer incidence monitoring Proceedings of the National Academy of Sciences of the United States of America High 23277562
2011 SMG1 activates p53 (Ser15 phosphorylation) in response to DNA double-strand breaks independently of the RNA surveillance proteins UPF1 and UPF2. In contrast, UPF1 and UPF2 (but not SMG1 alone) are required for p53 activation during persistent oxidative stress. Exogenously oxidized mRNA does not stimulate p53 activation, indicating SMG1's role is through DNA damage sensing, not RNA damage. siRNA knockdown of SMG1, UPF1, UPF2, ATM; expression of I-PpoI endonuclease (DSBs); in vitro mRNA oxidation/transfection; p53 Ser15 phosphorylation assay Cell cycle (Georgetown, Tex.) Medium 21701263
2013 SMG1 is involved in staufen1-mediated mRNA decay (SMD). SMG1 co-immunoprecipitates with Stau1, UPF1, and Dcp1a. Downregulation of SMG1 or expression of a kinase-inactive mutant inhibits SMD efficiency and impairs rapid degradation triggered by tethered Stau1 or Upf1. Stau1 and Upf1 colocalize in P-bodies in an SMG1-dependent manner. SMG1 levels increase during adipogenesis and SMG1 knockdown delays adipogenesis by reducing UPF1 phosphorylation. Co-immunoprecipitation, SMG1 knockdown, kinase-inactive mutant expression, SMD reporter assay, P-body colocalization imaging, adipogenesis differentiation assay Biochimica et biophysica acta Medium 24185201
2013 CK2-mediated phosphorylation of TEL2 increases SMG1 stability, which in turn increases UPF1 phosphorylation and augments NMD. Inhibition of CK2 or TEL2 downregulation impairs NMD and reduces SMG1-UPF1 complex formation and UPF1-bound PTC-containing mRNA. CK2 inhibition, TEL2 knockdown, SMG1 stability assay, UPF1 phosphorylation assay, NMD reporter, co-immunoprecipitation Biochimica et biophysica acta Medium 23831331
2011 SMG1 and NIK prevent Smac mimetic compound (SMC)-mediated apoptosis by maintaining c-FLIP levels to suppress caspase-8 activation. SMG1 in SMC-resistant cells represses SMC-mediated TNFα-induced JNK activation, sustaining c-FLIP levels. Depletion of SMG1 overcomes SMC-resistance by facilitating c-FLIP downregulation, leading to caspase-8-dependent apoptosis. siRNA functional screen (kinomic screen), SMG1 knockdown, caspase-8 activity assay, c-FLIP western blot, JNK activation assay Cell death & disease Medium 21490678
2013 MiRNA-125a and miRNA-125b are negative regulators of SMG1. They bind a microRNA response element in the 3'UTR of SMG1 mRNA, leading to SMG1 mRNA degradation. Overexpression of miR-125 suppresses endogenous SMG1 protein and represses the NMD pathway; knockdown of miR-125 upregulates NMD. miR-125 overexpression/knockdown, luciferase 3'UTR reporter assay, SMG1 protein and mRNA quantification, NMD reporter assay Biochemical and biophysical research communications Medium 23583196
2018 In Physcomitrella patens, SMG1 knockout reveals roles beyond mRNA quality control: smg1 knockout plants have increased susceptibility to DNA damage but increased tolerance to unfolded protein-inducing agents, suggesting SMG1 is involved in DNA repair and the unfolded protein response in addition to NMD. Analysis indicates splice junctions downstream of stop codons are the major determinant of NMD targeting. SMG1 knockout in moss, transcriptome-wide RNA-seq, DNA damage sensitivity assay, UPR tolerance assay, machine learning-assisted NMD targeting analysis Nucleic acids research Medium 29596649
2013 SMG1 knockdown via siRNA screen results in significant increases in pS129-phosphorylated α-synuclein, identifying SMG1 as a regulator of α-synuclein S129 phosphorylation. SMG1 protein levels are reduced in brain regions with high pS129 α-synuclein in dementia with Lewy bodies and Parkinson's disease with dementia. High-throughput siRNA screen (711 kinases, 206 phosphatases), high-content fluorescence assay for pS129 α-synuclein, immunohistochemistry in patient brain tissue PloS one Low 24204929
2022 IL-6/STAT3 signaling in tumor cells induces SMG1 expression, which limits the expression of frameshift neoantigen-encoding mRNAs under NMD control, thereby compromising anti-tumor immune responses. This was demonstrated using an in vivo NMD luciferase reporter and functional immunotherapy assays. NMD luciferase reporter in vivo, cytokine screening, in silico analysis, functional assays, murine tumor models, cancer immunotherapy experiments Molecular cancer Medium 36443756
2022 Loss-of-function mutations in SMG8 or SMG9 cause resistance to ATR inhibitors (ATRi) through an SMG1-mediated mechanism. SMG8/9-defective cells exhibit reduced ATRi-induced transcription/replication conflicts (TRCs), and characteristic ATRi responses (ATM/CHK2, γH2AX, phospho-RPA, 53BP1) are absent, establishing SMG8/9 as regulators of SMG1 activity in a DNA damage context. Genome-wide CRISPR-Cas9 positive selection screen, loss-of-function validation, ATRi treatment, DNA damage response markers (western blot), TRC measurement, cell cycle analysis Cancer research Medium 36273494

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Genetics of cleft lip and cleft palate. American journal of medical genetics. Part C, Seminars in medical genetics 330 24124047
2006 Development of the upper lip: morphogenetic and molecular mechanisms. Developmental dynamics : an official publication of the American Association of Anatomists 248 16292776
2007 Impaired FGF signaling contributes to cleft lip and palate. Proceedings of the National Academy of Sciences of the United States of America 234 17360555
2001 The rhombic lip and early cerebellar development. Current opinion in neurobiology 196 11179876
2008 Unraveling human cleft lip and palate research. Journal of dental research 191 18218836
2004 The complex genetics of cleft lip and palate. European journal of orthodontics 167 14994877
2010 CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability. Molecular cell 161 20864032
2010 Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay. Proceedings of the National Academy of Sciences of the United States of America 157 20566848
2006 SUMO1 haploinsufficiency leads to cleft lip and palate. Science (New York, N.Y.) 147 16990542
2001 Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. The Journal of biological chemistry 133 11331269
2022 Failure of human rhombic lip differentiation underlies medulloblastoma formation. Nature 117 36131014
2010 Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Developmental biology 115 20123092
2014 Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis. The Journal of clinical investigation 100 24590292
2004 SMG-1 is a phosphatidylinositol kinase-related protein kinase required for nonsense-mediated mRNA Decay in Caenorhabditis elegans. Molecular and cellular biology 97 15314158
1995 Outcome analysis for lip carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 97 7478649
2005 Progress toward discerning the genetics of cleft lip. Current opinion in pediatrics 93 16282779
2011 Genetics of syndromic and nonsyndromic cleft lip and palate. The Journal of craniofacial surgery 90 21959420
2002 The migration of cerebellar rhombic lip derivatives. Development (Cambridge, England) 85 12361964
2004 Current concepts in lip reconstruction. Current opinion in otolaryngology & head and neck surgery 81 15252247
2010 Lip cancer: incidence, trends, histology and survival: 1970-2006. The British journal of dermatology 80 20163415
2014 Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD. Structure (London, England : 1993) 70 25002321
2023 Orofacial Clefts: Genetics of Cleft Lip and Palate. Genes 66 37628654
2020 Circular RNA VMA21 ameliorates sepsis-associated acute kidney injury by regulating miR-9-3p/SMG1/inflammation axis and oxidative stress. Journal of cellular and molecular medicine 66 32827242
2019 LncRNA MAGI2-AS3 inhibits hepatocellular carcinoma cell proliferation and migration by targeting the miR-374b-5p/SMG1 signaling pathway. Journal of cellular physiology 66 30924168
2010 Folate pathway and nonsyndromic cleft lip and palate. Birth defects research. Part A, Clinical and molecular teratology 63 21254359
2021 Curcumin inhibits ovarian cancer progression by regulating circ-PLEKHM3/miR-320a/SMG1 axis. Journal of ovarian research 62 34784955
2012 Roles of BMP signaling pathway in lip and palate development. Frontiers of oral biology 62 22759670
2005 Characterization of mast cell subpopulations in lip cancer. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 60 15817069
2005 LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans. The EMBO journal 59 16319922
2008 Lip reconstruction. Seminars in plastic surgery 57 20567703
2012 Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proceedings of the National Academy of Sciences of the United States of America 54 23277562
2012 Antihypertensive drugs and lip cancer in non-Hispanic whites. Archives of internal medicine 53 22869299
2012 Wnt signaling in lip and palate development. Frontiers of oral biology 52 22759672
2006 Contributions of PTCH gene variants to isolated cleft lip and palate. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 51 16405370
1993 Carcinoma of the lip. Otolaryngologic clinics of North America 50 8460042
2012 Development of the lip and palate: FGF signalling. Frontiers of oral biology 48 22759671
2013 SMG1 is an ancient nonsense-mediated mRNA decay effector. The Plant journal : for cell and molecular biology 43 24103012
2015 The role of C/EBP-β LIP in multidrug resistance. Journal of the National Cancer Institute 42 25766403
1990 Lip reconstruction with motor and sensory innervated composite flaps. Clinics in plastic surgery 41 2249383
2016 The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. Nature communications 40 26841701
1999 Treatment outcome in cleft lip and palate: issues and perspectives. Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists 40 10759424
2019 MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma. Cell death & disease 38 31659158
2020 Targeting the estrogen receptor alpha (ERα)-mediated circ-SMG1.72/miR-141-3p/Gelsolin signaling to better suppress the HCC cell invasion. Oncogene 37 31996784
2004 The differentiation profile of the epithelium of the human lip. Archives of oral biology 37 15748696
1996 Expression of lip genes during growth in soil and oxidation of anthracene by Phanerochaete chrysosporium. Applied and environmental microbiology 36 8837425
2020 Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity. eLife 34 32469312
2019 Biomaterials for Cleft Lip and Palate Regeneration. International journal of molecular sciences 33 31052503
2014 MicroRNA expression profiling of the developing murine upper lip. Development, growth & differentiation 33 24849136
2011 The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA. Cell cycle (Georgetown, Tex.) 33 21701263
2007 Karapandzic flap for reconstruction of lip defects. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 33 18022478
2019 InsP6 binding to PIKK kinases revealed by the cryo-EM structure of an SMG1-SMG8-SMG9 complex. Nature structural & molecular biology 31 31792449
1991 Operations for microforms of cleft lip. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 31 1911818
2017 Upper Lip Reconstruction. Plastic and reconstructive surgery 30 28746241
2014 Deregulation of the endogenous C/EBPβ LIP isoform predisposes to tumorigenesis. Journal of molecular medicine (Berlin, Germany) 30 25401168
2017 SMG-1 inhibition by miR-192/-215 causes epithelial-mesenchymal transition in gastric carcinogenesis via activation of Wnt signaling. Cancer medicine 29 29239144
1998 Epidemiology of cancer of the lip in The Netherlands. Oral oncology 29 9861352
2022 IL-6/STAT3 signaling in tumor cells restricts the expression of frameshift-derived neoantigens by SMG1 induction. Molecular cancer 28 36443756
2010 Brachytherapy in lip carcinoma: long-term results. International journal of radiation oncology, biology, physics 28 21163589
1979 Carcinoma of the lip. Archives of otolaryngology (Chicago, Ill. : 1960) 28 426705
2019 MicroRNA-655-3p and microRNA-497-5p inhibit cell proliferation in cultured human lip cells through the regulation of genes related to human cleft lip. BMC medical genomics 27 31122291
2019 Cryo-EM structure of SMG1-SMG8-SMG9 complex. Cell research 27 31729466
2021 Cryo-EM reconstructions of inhibitor-bound SMG1 kinase reveal an autoinhibitory state dependent on SMG8. eLife 26 34698635
2011 SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds. Cell death & disease 26 21490678
2019 Current concepts on cleft lip and palate etiology. Journal of biological regulators and homeostatic agents 25 31538461
2014 SMG1 acts as a novel potential tumor suppressor with epigenetic inactivation in acute myeloid leukemia. International journal of molecular sciences 25 25257528
2018 Reduced expression of C/EBPβ-LIP extends health and lifespan in mice. eLife 24 29708496
2024 FLiPPR: A Processor for Limited Proteolysis (LiP) Mass Spectrometry Data Sets Built on FragPipe. Journal of proteome research 22 38787630
2020 Msx1 deficiency interacts with hypoxia and induces a morphogenetic regulation during mouse lip development. Development (Cambridge, England) 22 32467233
2013 MicroRNA 125 represses nonsense-mediated mRNA decay by regulating SMG1 expression. Biochemical and biophysical research communications 22 23583196
2011 Surgical management of lip cancer. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale 22 21808457
2018 Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS. Cell reports 21 29444422
2017 Lip leishmaniasis: a case series with molecular identification and literature review. BMC infectious diseases 21 28122496
2018 The loss of SMG1 causes defects in quality control pathways in Physcomitrella patens. Nucleic acids research 20 29596649
2017 Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma. Oral diseases 19 28107582
2014 Expression and significance of the novel tumor-suppressor gene SMG-1 in hepatocellular carcinoma. Oncology reports 19 24700316
2014 Functional Significance of MMP3 and TIMP2 Polymorphisms in Cleft Lip/Palate. Journal of dental research 19 24799419
2013 SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay. Biochimica et biophysica acta 19 24185201
2021 Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer. Frontiers in cell and developmental biology 18 34595165
2011 LIP expression is regulated by IGF-1R signaling and participates in suppression of anoikis. Molecular cancer 18 21854628
2018 Oral fibropapillomatosis and epidermal hyperplasia of the lip in newborn lambs associated with bovine Deltapapillomavirus. Scientific reports 17 30190493
2011 Lip cancer: retrospective analysis of 181 cases. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 17 22136191
2008 Salivary analysis and antioxidants in cleft lip and palate children. Archives of oral biology 17 18242578
1990 Reconstruction of the lip. Otolaryngologic clinics of North America 16 2259513
2020 LncRNA GAS5 sponges miR-362-5p to promote sensitivity of thyroid cancer cells to 131 I by upregulating SMG1. IUBMB life 15 32856394
2015 Structure of product-bound SMG1 lipase: active site gating implications. The FEBS journal 15 26365206
2013 CK2-mediated TEL2 phosphorylation augments nonsense-mediated mRNA decay (NMD) by increase of SMG1 stability. Biochimica et biophysica acta 15 23831331
2013 Expression of the high light-inducible Dunaliella LIP promoter in Chlamydomonas reinhardtii. Planta 15 24043576
1994 Multinucleate cell angiohistiocytoma of the upper lip. Oral surgery, oral medicine, and oral pathology 15 7898910
2022 SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance. Cancer research 14 36273494
2007 Describing cleft lip and palate using a new expression system. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 14 18177187
2021 HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis. Infectious agents and cancer 13 34389030
2020 MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1. Oncology letters 13 32565999
2019 Detection of cellular material in lip-prints. Forensic science, medicine, and pathology 13 30903586
2019 A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene. PLoS genetics 13 31469826
2015 Residue Asn277 affects the stability and substrate specificity of the SMG1 lipase from Malassezia globosa. International journal of molecular sciences 13 25837472
2012 Cells expressing the C/EBPbeta isoform, LIP, engulf their neighbors. PloS one 13 22860016
2013 SMG1 identified as a regulator of Parkinson's disease-associated alpha-synuclein through siRNA screening. PloS one 12 24204929
2003 Paying more than lip service to lip lesions. Canadian family physician Medecin de famille canadien 12 14526863
2017 C/EBPβ LIP augments cell death by inducing osteoglycin. Cell death & disease 11 28383550
2015 VEGFR1 and VEGFR2 in lip carcinogenesis and its association with microvessel density. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 25895461

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