Affinage

SND1

Staphylococcal nuclease domain-containing protein 1 · UniProt Q7KZF4

Round 2 corrected
Length
910 aa
Mass
102.0 kDa
Annotated
2026-04-28
130 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SND1 is a multidomain RNA- and protein-binding scaffold that integrates transcriptional coactivation, pre-mRNA splicing, mRNA stability control, and immune evasion across nuclear, cytoplasmic, ER-membrane, and mitochondrial compartments. In the nucleus, SND1 bridges sequence-specific transcription factors (STAT6, c-Myb, Smad2/3/4) to RNA polymerase II and recruits the histone acetyltransferase GCN5 to target promoters, while its Tudor (TSN) domain engages methylated spliceosomal snRNP components to accelerate spliceosome assembly and direct alternative splicing of transcripts such as CD44 in concert with SAM68 (PMID:12234934, PMID:28263968, PMID:17576664, PMID:23995791). SND1 functions as an N6-methyladenosine (m⁶A) RNA reader that stabilizes both viral (KSHV ORF50, SARS-CoV-2) and cellular (Nrf2, AT1R) transcripts, and as a Tudor-domain nuclease that, together with UPF1, degrades AGO2-loaded miRNAs via TumiD (PMID:31647415, PMID:37794589, PMID:28827400, PMID:18603592). At the endoplasmic reticulum, SND1 is anchored through SEC61A and diverts nascent MHC-I heavy chains to ERAD, while its complex with MTDH destabilizes Tap1/2 mRNAs, jointly suppressing antigen presentation — a mechanism now pharmacologically targetable with small-molecule inhibitors that synergize with anti-PD-1 immunotherapy (PMID:32917674, PMID:35121988, PMID:35121987).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing SND1 as a transcriptional coactivator: SND1 was linked to signal-dependent gene activation when it was shown to form a Pim-1-phosphorylated complex that potentiates c-Myb transcriptional activity downstream of Ras signaling.

    Evidence Yeast two-hybrid, in vitro kinase assay, co-IP, and reporter assays in mammalian cells

    PMID:9809063

    Open questions at the time
    • Phosphorylation sites on SND1 by Pim-1 not mapped
    • Whether phosphorylation is required for coactivator function was not tested
  2. 2002 High

    The coactivator mechanism was generalized when SND1's SN-like domain was shown to bridge STAT6 to RNA polymerase II, establishing it as a modular adaptor for cytokine-induced transcription.

    Evidence Reciprocal co-IP, in vitro binding, domain mapping, IL-4-induced Igε reporter assay

    PMID:12234934

    Open questions at the time
    • Structural basis of SN-domain interaction with STAT6 TAD not resolved
    • Whether other STATs use the same interface was untested
  3. 2007 High

    SND1 was revealed to have a dual nuclear function — beyond transcription, its Tudor (TSN) domain directly accelerates spliceosome assembly by engaging methylated snRNP components, a mechanism explained at atomic resolution by crystallography.

    Evidence In vitro reconstituted splicing assay with purified SND1/TSN domain; X-ray crystal structure of TSN domain with snRNP peptides

    PMID:17576664 PMID:17632523

    Open questions at the time
    • Identity of specific snRNP methylation marks required in vivo not defined
    • Relative contribution of splicing vs. transcription roles to cellular phenotype unclear
  4. 2008 Medium

    SND1 was shown to possess an RISC/AGO2-independent mRNA-stabilizing activity, binding the AT1R 3′-UTR via its SN domains to reduce mRNA decay and enhance translation, broadening its function to post-transcriptional gene regulation.

    Evidence RNA pull-down, mRNA decay assay, overexpression/knockdown, domain deletion mapping

    PMID:18603592

    Open questions at the time
    • Transcriptome-wide scope of SND1-mediated mRNA stabilization not yet mapped
    • Mechanism by which SN domains protect mRNA from decay not defined
  5. 2011 High

    The discovery of the MTDH–SND1 interaction established SND1 as a key oncogenic effector: the complex promotes lung metastasis and sustains tumor-initiating cells in breast cancer.

    Evidence Mass spectrometry interactome, co-IP, shRNA knockdown, in vivo metastasis assay in mouse models

    PMID:21478147 PMID:24981741

    Open questions at the time
    • How MTDH stabilizes SND1 at the molecular level was not resolved at this stage
    • Cell-type specificity of MTDH-SND1 oncogenic function unexplored
  6. 2014 High

    The structural basis of the MTDH–SND1 complex was determined at high resolution, revealing a two-tryptophan anchor of MTDH in the SN1/2 groove of SND1 — providing the template for pharmacological disruption.

    Evidence X-ray crystallography, site-directed mutagenesis with functional validation in cancer cells

    PMID:25242325

    Open questions at the time
    • Whether endogenous post-translational modifications modulate the interface was unknown
    • No small-molecule inhibitors yet existed
  7. 2013 Medium

    SND1's splicing function was connected to cancer biology when it was shown to recruit SAM68 and spliceosomal components to CD44 pre-mRNA, promoting inclusion of variable exons that drive prostate cancer cell proliferation and migration.

    Evidence Reciprocal co-IP, RNA immunoprecipitation, alternative splicing RT-PCR, siRNA knockdown with migration/proliferation assays

    PMID:23995791

    Open questions at the time
    • Full set of SND1-regulated alternative splicing events in cancer not catalogued
    • Whether SAM68 is required for all SND1 splicing targets unknown
  8. 2015 High

    SND1 was placed within the TGFβ signaling cascade: Smad2/3 directly activates SND1 transcription, and SND1 in turn promotes Smurf1-mediated RhoA degradation, connecting SND1 to cytoskeletal remodeling and metastasis.

    Evidence ChIP on SND1 promoter, reporter assay, co-IP, siRNA epistasis, in vivo metastasis model

    PMID:25596283

    Open questions at the time
    • Whether SND1 directly activates Smurf1 transcription or acts post-transcriptionally was not resolved
    • Generalizability beyond breast cancer metastasis models untested
  9. 2017 High

    The nuclease activity of SND1 was functionally contextualized: SND1's Tudor domain cooperates with UPF1 to degrade AGO2-loaded miRNAs (TumiD), with ~50% of TumiD targets being UPF1-dependent, linking SND1-mediated miRNA decay to cancer cell invasion.

    Evidence In vitro nuclease reconstitution with AGO2-loaded miRNAs, genome-wide miR-seq, siRNA knockdown, cell invasion assay

    PMID:28827400

    Open questions at the time
    • Structural basis for how UPF1 renders miRNAs accessible to SND1 nuclease activity unresolved
    • In vivo physiological relevance of TumiD in non-cancer contexts unknown
  10. 2017 High

    SND1's transcriptional coactivation mechanism was further refined: the Tudor domain recruits GCN5 to Smad promoters, increasing H3K9 acetylation and creating a positive feedback loop within TGFβ signaling.

    Evidence EMSA for direct DNA binding, GST pulldown for Tudor-GCN5 interaction, ChIP for H3K9ac, siRNA knockdown

    PMID:28263968

    Open questions at the time
    • Whether SND1-GCN5 recruitment extends beyond Smad promoters not mapped genome-wide
    • Structural details of Tudor-GCN5 interface unknown
  11. 2019 High

    SND1 was identified as an m⁶A RNA reader, establishing a new molecular activity: SND1 preferentially binds m⁶A-modified RNAs including KSHV ORF50 to stabilize them, a function essential for viral lytic replication.

    Evidence RIP-seq, eCLIP, m⁶A-modified vs. unmodified RNA pulldown, siRNA knockdown with viral replication assay

    PMID:31647415

    Open questions at the time
    • Structural basis for m⁶A recognition by SND1 not determined
    • Whether m⁶A reading uses the same domain as other RNA-binding activities was unclear
  12. 2020 High

    SND1 was found to suppress antigen presentation from the ER: anchored to the ER membrane via SEC61A, it diverts nascent MHC-I heavy chains to ERAD, and its deletion in tumor-bearing mice restores surface MHC-I and increases CD8⁺ T cell infiltration.

    Evidence Subcellular fractionation, co-IP with SEC61A and MHC-I HC, ERAD assay, in vivo OT-I mouse model, flow cytometry

    PMID:32917674

    Open questions at the time
    • Whether SND1 acts catalytically or as a chaperone in ERAD not distinguished
    • Relationship between ER-localized SND1 and nuclear SND1 pools not established
  13. 2021 High

    The MTDH–SND1 complex was shown to suppress antigen presentation through a second, RNA-level mechanism — destabilizing Tap1/2 mRNAs — and small-molecule disruptors of this complex synergized with anti-PD-1 therapy, validating pharmacological targetability.

    Evidence Small-molecule PPI inhibitors (C26-A6), RIP for Tap1/2 mRNAs, mRNA stability assay, FACS, genetic mouse models, combination immunotherapy in vivo

    PMID:35121987 PMID:35121988

    Open questions at the time
    • Selectivity and pharmacokinetic profiles of C26 compounds for clinical translation incomplete
    • Whether Tap1/2 mRNA destabilization requires m⁶A reading function not tested
  14. 2022 Medium

    SND1 was localized to mitochondria via an N-terminal targeting sequence imported through TOM70, where it interacts with PGAM5 to facilitate DRP1-dependent mitophagy under stress — adding a mitochondrial dimension to its functions.

    Evidence Mitochondrial fractionation, IP-MS, MTS deletion mutant, FCCP-induced mitophagy assay, in vivo tumor growth

    PMID:35433434

    Open questions at the time
    • How the same N-terminal sequence mediates both ER anchoring and mitochondrial import is unresolved
    • Whether mitochondrial SND1 retains RNA-binding or nuclease activity unknown
  15. 2023 High

    SND1 was established as a host factor essential for SARS-CoV-2 RNA synthesis: it binds the 5′-end of negative-sense viral RNA, directly interacts with NSP9, and remodels NSP9 occupancy at replication-transcription initiation sites.

    Evidence iCLIP/eCLIP, co-IP with NSP9, siRNA depletion with viral kinetics and EM of replication organelles

    PMID:37794589

    Open questions at the time
    • Whether SND1's m⁶A-reading function contributes to SARS-CoV-2 RNA binding not resolved
    • Structural basis of SND1-NSP9 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: how a single protein distributes among nuclear, ER, and mitochondrial pools; the structural basis of m⁶A recognition; and whether the nuclease, m⁶A-reading, and mRNA-stabilizing activities are executed by the same or distinct domain configurations.
  • No unified model for SND1 subcellular partitioning
  • m⁶A reader domain identity not structurally defined
  • Relative contributions of SND1's multiple activities to tumorigenesis not dissected genetically in a single system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 2 GO:0003677 DNA binding 1 GO:0042393 histone binding 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 3 GO:0005783 endoplasmic reticulum 2 GO:0005739 mitochondrion 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 1
Partners
GCN5MTDHPGAM5PIM1SAM68SEC61A1STAT6UPF1
Complex memberships
MTDH-SND1 complexRISCTumiD (TSN-UPF1 miRNA decay complex)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Pim-1 kinase was found to interact with p100 (SND1) via yeast two-hybrid screen; Pim-1 phosphorylated p100 in vitro, formed a stable complex with p100 in animal cells, and functioned downstream of Ras to stimulate c-Myb transcriptional activity in a p100-dependent manner, establishing p100/SND1 as a transcriptional coactivator linking cytokine signaling to c-Myb activity. Yeast two-hybrid screen, in vitro phosphorylation assay, co-immunoprecipitation, transactivation assay Molecular cell High 9809063
2002 p100/SND1 was identified as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II. The interaction was mediated by the TAD domain of STAT6 and the SN-like domain of p100. p100 enhanced STAT6-mediated transcriptional activation and IL-4-induced Igε gene transcription, and associated with the large subunit of RNA polymerase II. Co-immunoprecipitation, in vitro interaction assay, reporter gene assay, domain mapping The EMBO journal High 12234934
2007 The TSN domain of p100/SND1 specifically interacts with components of the U5 snRNP and other spliceosomal snRNPs. Purified p100 and its isolated TSN domain accelerated spliceosome complex A formation and the A-to-B transition in vitro, and enhanced the kinetics of the first splicing step in a dose-dependent manner, revealing a dual role in transcription and pre-mRNA splicing. Co-immunoprecipitation, in vitro splicing assay, domain-specific pull-down Nucleic acids research High 17576664
2007 Crystal structure of the p100/SND1 TSN domain was determined, revealing an interdigitated hook-like structure with a conserved aromatic cage that hooks methyl groups of snRNP proteins, providing structural explanation for SND1's roles in transcription and spliceosome anchoring. X-ray crystallography, structural analysis of Tudor-SN domain with snRNP peptides Nature structural & molecular biology High 17632523
2007 SND1 was identified as a component of the RNA-induced silencing complex (RISC) and was shown to be up-regulated in human colon cancers. Overexpression of SND1 in intestinal epithelial cells caused loss of contact inhibition, promoted cell growth, altered E-cadherin distribution, and down-regulated APC protein (without altering APC mRNA), implicating SND1-mediated post-transcriptional regulation in colon carcinogenesis. Stable overexpression, cell proliferation assay, immunofluorescence, Western blot, immunohistochemistry Cancer research Medium 17909068
2008 p100/SND1 was found to bind the angiotensin II type 1 receptor (AT1R) 3'-UTR via its SN-like domains, increasing AT1R expression by decreasing mRNA decay rate and enhancing translation. This effect was independent of Argonaute2/RISC, revealing a novel mRNA-stabilizing function of SND1. RNA pull-down, p100 silencing, overexpression, mRNA decay assay, deletion mapping of binding site Nucleic acids research Medium 18603592
2010 Cellular p100/SND1 was identified as a host factor that binds the dengue virus 3'-UTR (specifically the A4 stem-loop region). p100 knockdown reduced viral RNA levels and viral protein expression, and decreased expression of a luciferase-3'UTR(DENV) reporter in an A4-dependent manner, demonstrating that SND1 is required for normal dengue virus replication. RNA affinity capture, mass spectrometry, RNA immunoprecipitation, confocal immunofluorescence, siRNA knockdown, luciferase reporter assay The Journal of general virology Medium 21148275
2011 SND1 was identified as a MTDH (Metadherin)-interacting protein by mass spectrometry-based screen. SND1 strongly promotes lung metastasis in breast cancer models and promotes resistance to apoptosis. Silencing SND1 reduced metastatic potential and regulated expression of genes associated with metastasis and chemoresistance. Mass spectrometry interactome screen, co-immunoprecipitation, shRNA knockdown, in vivo metastasis assay The Journal of biological chemistry Medium 21478147
2013 SND1 was found to interact with SAM68 in prostate cancer cells. SND1 upregulation synergizes with SAM68 to promote inclusion of CD44 variable exons. SND1 promotes inclusion of CD44 variable exons by recruiting SAM68 and spliceosomal components to CD44 pre-mRNA. Knockdown of SND1 reduced proliferation and migration of prostate cancer cells. Mass spectrometry, co-immunoprecipitation, RNA immunoprecipitation, siRNA knockdown, alternative splicing analysis, cell migration/proliferation assays Oncogene Medium 23995791
2014 High-resolution crystal structure of the MTDH-SND1 complex was determined, revealing that an 11-residue MTDH peptide motif occupies an extended groove between SND1's SN1/2 domains, with two MTDH tryptophan residues nestled into two pockets in SND1. Mutations at both tryptophan-binding pockets impaired MTDH-SND1 interactions and their roles in breast cancer, and also impaired SND1 stability under stress. X-ray crystallography, site-directed mutagenesis, co-immunoprecipitation, cancer cell functional assays Cell reports High 25242325
2014 MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells (TICs) in mammary tumors. Mechanistically, MTDH supports survival of mammary epithelial cells under oncogenic/stress conditions by interacting with and stabilizing SND1. Silencing MTDH or SND1 individually, or disrupting their interaction, compromised tumorigenic potential of TICs in vivo. Mouse mammary tumor models, genetic knockdown, co-immunoprecipitation, tumor-initiating cell assays in vivo Cancer cell High 24981741
2015 SND1 acts downstream of TGFβ1 and upstream of Smurf1 to promote breast cancer metastasis. TGFβ1/Smad2/Smad3 complex transcriptionally activates SND1 via Smad recognition domains (RD motifs) in the SND1 promoter. SND1 promotes Smurf1 expression, leading to RhoA ubiquitination and degradation, disrupting F-actin organization, reducing cell adhesion, and increasing cell migration and invasion. Promoter analysis, ChIP, reporter assay, co-immunoprecipitation, siRNA knockdown, cell migration/invasion assays, in vivo metastasis model Cancer research High 25596283
2016 SND1 promotes hepatocarcinogenesis by interacting with and inducing ubiquitination and proteasomal degradation of monoglyceride lipase (MGLL), a tumor suppressor. MGLL overexpression inhibited HCC cell proliferation and tumor growth, and inhibited Akt activation independently of MGLL's enzymatic activity. Yeast two-hybrid assay, co-immunoprecipitation, ubiquitination assay, cell proliferation assay, in vivo xenograft assay, IHC of tissue microarray The Journal of biological chemistry Medium 26997225
2017 SND1 physically associates with and recruits the histone acetyltransferase GCN5 to the promoter regions of Smad2/3/4, enhancing their transcriptional activation. EMSA confirmed SND1 binds conserved motifs (motifs 1 and 2) in Smad gene promoters. GST pulldown assays showed the Tudor domain of SND1 is responsible for GCN5 recruitment, which increases histone H3K9 acetylation. Loss-of-function of SND1 reduced Smad protein levels and phosphorylation of R-Smads, attenuating TGFβ signaling. EMSA, GST pulldown, ChIP, co-immunoprecipitation, siRNA knockdown, histone acetylation assay Oncogene High 28263968
2019 SND1 is identified as an m6A RNA reader. RIP-seq and eCLIP characterised SND1's transcriptome-wide RNA binding profile. The m6A modification of KSHV ORF50 RNA is critical for SND1 binding, which stabilises the ORF50 transcript. SND1 depletion inhibits KSHV early gene expression and is essential for KSHV lytic replication. RIP-seq, eCLIP, m6A-modified RNA pulldown, siRNA knockdown, viral replication assays eLife High 31647415
2019 SND1 facilitates invasion and migration of cervical cancer cells via Smurf1-mediated ubiquitination and degradation of FOXA2. SND1 knockdown inhibited EMT and lung metastasis in vivo. The pro-metastatic effect of SND1 was dependent on FOXA2 inhibition through Smurf1-mediated degradation. siRNA knockdown, co-immunoprecipitation, ubiquitination assay, xenograft assay, cell migration/invasion assays Experimental cell research Medium 31891682
2019 PTB-AS (a natural antisense noncoding RNA) promotes PTBP1 mRNA stability by directly binding to its 3'-UTR, and SND1 dramatically increases the binding capacity between PTB-AS and PTBP1 mRNA, masking the miR-9 binding site. This reveals a role for SND1 in facilitating lncRNA-mRNA interactions to stabilize target mRNAs. RNA immunoprecipitation, siRNA knockdown, mRNA stability assay, luciferase reporter assay Molecular therapy Low 31253583
2020 SND1 oncoprotein is identified as an endoplasmic reticulum (ER) membrane-associated protein. The N-terminal peptide of SND1 associates with SEC61A, anchoring SND1 on the ER membrane. The SN domain of SND1 catches and guides nascent MHC-I heavy chain (HC) to ER-associated degradation (ERAD), hindering normal MHC-I assembly. Deletion of SND1 in tumor-bearing mice promotes MHC-I surface presentation and increases CD8+ T cell infiltration. Subcellular fractionation, co-immunoprecipitation, ERAD assay, domain mapping, in vivo transgenic mouse model (OT-I), flow cytometry Science advances High 32917674
2021 Pharmacological disruption of the MTDH-SND1 complex with small-molecule compound C26-A6 enhances tumor antigen presentation and synergizes with anti-PD-1 therapy. Mechanistically, the MTDH-SND1 complex reduces antigen presentation by binding to and destabilizing Tap1/2 mRNAs, which encode key components of the antigen-presentation machinery. Small-molecule compound treatment, RNA immunoprecipitation, mRNA stability assay, FACS (antigen presentation), in vivo tumor models combined with anti-PD-1 Nature cancer High 35121988
2021 Genetic ablation of Mtdh in mouse models inhibits breast cancer development through disruption of its interaction with SND1. Small-molecule inhibitors C26-A2 and C26-A6 that specifically disrupt the MTDH-SND1 protein-protein interaction suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical TNBC models. Genetically modified mouse models, small-molecule PPI inhibitor screen, co-immunoprecipitation, in vivo tumor models Nature cancer High 35121987
2022 SND1 is localized to mitochondria via an N-terminal mitochondrial targeting sequence (amino acids 1-63), imported through TOM70. In mitochondria, SND1 interacts with PGAM5 and is crucial for PGAM5-DRP1 binding. SND1-mediated mitophagy under stress conditions (FCCP treatment, glucose deprivation) requires both PGAM5 and the SND1 mitochondrial targeting sequence. Organelle subcellular isolation, mass spectrometry, co-immunoprecipitation (IP-MS), mitophagy assay (FCCP treatment), domain deletion (MTS mutant), in vitro and in vivo tumor growth assays Frontiers in oncology Medium 35433434
2023 SND1 binds the 5'-end of SARS-CoV-2 negative-sense viral RNA and is required for viral RNA synthesis. SND1-depleted cells form smaller replication organelles and show diminished virus growth kinetics. SND1 directly interacts with the viral RNA-binding protein NSP9 and remodels NSP9 occupancy on viral RNA, altering NSP9's covalent linkage to initiating nucleotides at replication-transcription initiation sites. Biochemical RNA-protein interaction mapping, iCLIP/eCLIP, co-immunoprecipitation, siRNA depletion, electron microscopy of replication organelles, viral replication kinetics assay Cell High 37794589
2023 SNAI3-AS1 lncRNA competitively binds SND1 and perturbs m6A-dependent recognition of Nrf2 mRNA 3'-UTR by SND1, thereby reducing Nrf2 mRNA stability. SND1 overexpression rescues ferroptosis resistance phenotypes lost upon SNAI3-AS1 overexpression, placing SND1 as an m6A reader that stabilizes Nrf2 mRNA in glioma. RNA pulldown, RIP, MeRIP (m6A-IP), dual-luciferase reporter assay, gain/loss-of-function rescue experiments, in vitro and in vivo ferroptosis assays Journal of experimental & clinical cancer research Medium 37202791
2017 TSN (Tudor-SN/SND1)-mediated miRNA decay (TumiD) requires the RNA helicase UPF1 in cellular contexts. UPF1 dissociates miRNAs from their mRNA targets, making AGO2-loaded miRNAs susceptible to TSN-mediated nuclease degradation. Deep miRNA sequencing showed ~50% of candidate TumiD targets are augmented by UPF1, and UPF1-augmented TumiD promotes cancer cell invasion by degrading anti-invasive miRNAs. In vitro TSN nuclease assay with AGO2-loaded miRNAs, miR-seq (deep sequencing), siRNA knockdown of UPF1, cell invasion assay Genes & development High 28827400
2012 A chromosomal rearrangement between 7q32 and 7q34 generates an SND1-BRAF fusion protein in c-Met inhibitor-resistant gastric cancer cells. The SND1-BRAF fusion is constitutively active, hyperactivates the downstream MAPK pathway, and confers resistance to c-Met receptor tyrosine kinase inhibition. Combination treatment with a BRAF or MEK inhibitor circumvented resistance. Chromosomal rearrangement characterization, Western blot (ERK/MEK phosphorylation), ectopic expression, drug resistance assay PloS one Medium 22745804
2000 The p100/SND1 coactivator protein was identified in endoplasmic reticulum and cytosolic lipid droplets of milk-secreting cells, in addition to its known nuclear localization. Immunofluorescence microscopy confirmed non-nuclear localization in mammary epithelial cells. The abundance of p100 was increased in the lactating state by a post-transcriptional mechanism (without change in mRNA levels), suggesting regulated subcellular distribution. Subcellular fractionation, immunofluorescence microscopy, Western blot Biochimica et biophysica acta Low 11099861
2015 LncRNA-HIT forms a nuclear complex with p100 (SND1) and CBP in limb mesenchyme. ChIRP-seq revealed LncRNA-HIT-p100/CBP complexes associate with multiple loci involved in chondrogenic differentiation. siRNA reduction of p100 significantly decreased expression of LncRNA-HIT-associated chondrogenic loci and impacted H3K27ac, establishing SND1 as a component of a lncRNA-guided epigenetic regulatory complex required for chondrogenesis. Co-immunoprecipitation (nuclear complex), ChIRP-seq, siRNA knockdown, histone acetylation (H3K27ac) measurement, cartilage nodule formation assay PLoS genetics Medium 26633036

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2001 NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Molecular cell 694 11239468
2012 A census of human soluble protein complexes. Cell 689 22939629
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2007 The MYB46 transcription factor is a direct target of SND1 and regulates secondary wall biosynthesis in Arabidopsis. The Plant cell 448 17890373
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. Journal of proteome research 422 20020773
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2009 MYB83 is a direct target of SND1 and acts redundantly with MYB46 in the regulation of secondary cell wall biosynthesis in Arabidopsis. Plant & cell physiology 363 19808805
2015 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. The EMBO journal 362 25796446
2002 CD40 regulates the processing of NF-kappaB2 p100 to p52. The EMBO journal 350 12374738
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
1998 Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses. The Journal of experimental medicine 298 9432976
2003 TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation. The Journal of biological chemistry 277 12840022
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2007 Two NAC domain transcription factors, SND1 and NST1, function redundantly in regulation of secondary wall synthesis in fibers of Arabidopsis. Planta 267 17333250
2003 The IkappaB function of NF-kappaB2 p100 controls stimulated osteoclastogenesis. The Journal of experimental medicine 231 12939342
1998 Pim-1 kinase and p100 cooperate to enhance c-Myb activity. Molecular cell 217 9809063
2001 RelB cellular regulation and transcriptional activity are regulated by p100. The Journal of biological chemistry 168 11687592
2012 Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature cell biology 154 22388891
2002 Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II. The EMBO journal 146 12234934
2009 Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2). The Journal of biological chemistry 143 20038584
2006 Rescue of TRAF3-null mice by p100 NF-kappa B deficiency. The Journal of experimental medicine 143 17015635
1995 p120, a p120-related protein (p100), and the cadherin/catenin complex. The Journal of cell biology 136 7615637
2003 NF- kappa B2/p100 induces Bcl-2 expression. Leukemia 133 12835724
2009 The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Molecular cell 130 19524538
2003 RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. The Journal of biological chemistry 130 12709443
2020 A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors. Genomics 125 32645525
2009 NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism. The Journal of clinical investigation 124 19770515
2006 Stat3 activation of NF-{kappa}B p100 processing involves CBP/p300-mediated acetylation. Proceedings of the National Academy of Sciences of the United States of America 124 16651533
2012 Splice variant of the SND1 transcription factor is a dominant negative of SND1 members and their regulation in Populus trichocarpa. Proceedings of the National Academy of Sciences of the United States of America 120 22915581
2014 MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors. Cancer cell 118 24981741
2019 The Tudor SND1 protein is an m6A RNA reader essential for replication of Kaposi's sarcoma-associated herpesvirus. eLife 110 31647415
2011 Identification of staphylococcal nuclease domain-containing 1 (SND1) as a Metadherin-interacting protein with metastasis-promoting functions. The Journal of biological chemistry 105 21478147
2007 Transcriptional co-activator protein p100 interacts with snRNP proteins and facilitates the assembly of the spliceosome. Nucleic acids research 104 17576664
2007 SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis. Cancer research 101 17909068
2005 beta-TrCP binding and processing of NF-kappaB2/p100 involve its phosphorylation at serines 866 and 870. Cellular signalling 87 16303288
1996 Differential regulation of NF-kappaB2(p100) processing and control by amino-terminal sequences. Molecular and cellular biology 87 8887665
2015 SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis. Cancer research 86 25596283
2003 Epstein-Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-kappaB2 to p52 via an IKKgamma/NEMO-independent signalling pathway. Oncogene 84 14576817
2014 Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood 82 25237204
2013 The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells. Oncogene 81 23995791
2005 Stabilization of basally translated NF-kappaB-inducing kinase (NIK) protein functions as a molecular switch of processing of NF-kappaB2 p100. The Journal of biological chemistry 80 16223731
1993 NF-kappa B precursor p100 inhibits nuclear translocation and DNA binding of NF-kappa B/rel-factors. Oncogene 79 8336950
2014 Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness. Neuro-oncology 71 25216670
2007 The multifunctional human p100 protein 'hooks' methylated ligands. Nature structural & molecular biology 65 17632523
1994 Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs. Proceedings of the National Academy of Sciences of the United States of America 63 7809091
2008 Stabilization of RelB requires multidomain interactions with p100/p52. The Journal of biological chemistry 61 18321863
1999 Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli. The Biochemical journal 59 10024525
2021 Pharmacological disruption of the MTDH-SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer. Nature cancer 58 35121988
2008 p100 increases AT1R expression through interaction with AT1R 3'-UTR. Nucleic acids research 58 18603592
2002 NF-kappa B2 p100 is a pro-apoptotic protein with anti-oncogenic function. Nature cell biology 55 12389034
2004 Regulation of NF-kappa B2 p100 processing by its cis-acting domain. The Journal of biological chemistry 54 15485830
2021 Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis. Nature cancer 52 35121987
2014 p100/IκBδ sequesters and inhibits NF-κB through kappaBsome formation. Proceedings of the National Academy of Sciences of the United States of America 52 25349408
2015 LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes. PLoS genetics 50 26633036
2020 Oncoprotein SND1 hijacks nascent MHC-I heavy chain to ER-associated degradation, leading to impaired CD8+ T cell response in tumor. Science advances 47 32917674
2017 SND1 acts as a novel gene transcription activator recognizing the conserved Motif domains of Smad promoters, inducing TGFβ1 response and breast cancer metastasis. Oncogene 47 28263968
2005 High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins. Virology 47 15629778
2003 Critical role of RelB serine 368 for dimerization and p100 stabilization. The Journal of biological chemistry 47 12874295
2012 A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation. PloS one 46 22745804
2004 Tax deregulation of NF-kappaB2 p100 processing involves both beta-TrCP-dependent and -independent mechanisms. The Journal of biological chemistry 46 15310758
1997 Dephosphorylation of the cadherin-associated p100/p120 proteins in response to activation of protein kinase C in epithelial cells. The Journal of biological chemistry 46 9395537
2010 Functional interaction between cellular p100 and the dengue virus 3' UTR. The Journal of general virology 44 21148275
2023 Epigenetically silenced lncRNA SNAI3-AS1 promotes ferroptosis in glioma via perturbing the m6A-dependent recognition of Nrf2 mRNA mediated by SND1. Journal of experimental & clinical cancer research : CR 43 37202791
2018 SND1 acts as an anti-apoptotic factor via regulating the expression of lncRNA UCA1 in hepatocellular carcinoma. RNA biology 42 30321081
2010 Translational repression by the oocyte-specific protein P100 in Xenopus. Developmental biology 42 20471969
2019 Preventing abnormal NF-κB activation and autoimmunity by Otub1-mediated p100 stabilization. Cell research 41 31086255
1993 Isoforms p69 and p100 of 2',5'-oligoadenylate synthetase induced differentially by interferons in vivo and in vitro. Journal of interferon research 41 8454907
1992 Gene for the major antigenic structural protein (p100) of human herpesvirus 6. Journal of virology 41 1374813
2020 LncRNA LINC00665 Promotes Prostate Cancer Progression via miR-1224-5p/SND1 Axis. OncoTargets and therapy 40 32273723
2014 Structural insights into the tumor-promoting function of the MTDH-SND1 complex. Cell reports 40 25242325
2022 Circ_0004087 interaction with SND1 promotes docetaxel resistance in prostate cancer by boosting the mitosis error correction mechanism. Journal of experimental & clinical cancer research : CR 39 35659274
2008 SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing. EMBO reports 38 18617892
2009 NF-kappaB signalling proteins p50/p105, p52/p100, RelA, and IKKepsilon are over-expressed in oesophageal squamous cell carcinomas. Pathology 37 20001340
2000 Nuclear coactivator protein p100 is present in endoplasmic reticulum and lipid droplets of milk secreting cells. Biochimica et biophysica acta 37 11099861
2016 Staphylococcal Nuclease and Tudor Domain Containing 1 (SND1 Protein) Promotes Hepatocarcinogenesis by Inhibiting Monoglyceride Lipase (MGLL). The Journal of biological chemistry 36 26997225
2015 Common Oncogene Mutations and Novel SND1-BRAF Transcript Fusion in Lung Adenocarcinoma from Never Smokers. Scientific reports 36 25985019
2002 Is NF-kappaB2/p100 a direct activator of programmed cell death? Cancer cell 36 12498710
1997 The complement-activating protease P100 is expressed by hepatocytes and is induced by IL-6 in vitro and during the acute phase reaction in vivo. Laboratory investigation; a journal of technical methods and pathology 36 9314946
2003 Regulation of NF-kappaB2/p100 processing by its nuclear shuttling. Oncogene 35 12894228
2018 Insights Into SND1 Oncogene Promoter Regulation. Frontiers in oncology 34 30619748
2010 MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis. Mutation research 34 20883704
2001 The p100 coactivator is present in the nuclei of mammary epithelial cells and its abundance is increased in response to prolactin in culture and in mammary tissue during lactation. The Journal of endocrinology 34 11691653
2008 Lack of nuclear factor-kappa B2/p100 causes a RelB-dependent block in early B lymphopoiesis. Blood 33 18505785
2007 Negative regulation of TCR signaling by NF-kappaB2/p100. Journal of immunology (Baltimore, Md. : 1950) 32 17548614
2023 SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9. Cell 31 37794589
2015 Tumor-suppressor NFκB2 p100 interacts with ERK2 and stabilizes PTEN mRNA via inhibition of miR-494. Oncogene 31 26686085
2019 PTB-AS, a Novel Natural Antisense Transcript, Promotes Glioma Progression by Improving PTBP1 mRNA Stability with SND1. Molecular therapy : the journal of the American Society of Gene Therapy 30 31253583
2017 UPF1 helicase promotes TSN-mediated miRNA decay. Genes & development 30 28827400
2011 Nuclear factor-κB2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1α independent manner. Laboratory investigation; a journal of technical methods and pathology 30 21537326
2016 The NF-κB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100. Science signaling 27 27678221
1987 Normal temporal variability of the P100. Electroencephalography and clinical neurophysiology 27 2435531
2021 Circ SMARCA5 Inhibited Tumor Metastasis by Interacting with SND1 and Downregulating the YWHAB Gene in Cervical Cancer. Cell transplantation 26 33588586
2019 SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2. Experimental cell research 26 31891682
2017 A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs. The EMBO journal 26 29061763
2005 Meiotic messenger RNA and noncoding RNA targets of the RNA-binding protein Translin (TSN) in mouse testis. Biology of reproduction 26 15987823
1998 Regulation of p100 (NFKB2) expression in human monocytes in response to inflammatory mediators and lymphokines. Leukemia 26 9529131
2021 Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility. The Journal of experimental medicine 24 33107914
2012 Balance between NF-κB p100 and p52 regulates T cell costimulation dependence. Journal of immunology (Baltimore, Md. : 1950) 24 23248260
2010 Association of SND1 protein to low density lipid droplets in liver steatosis. Journal of physiology and biochemistry 24 20414760
2018 miR-361-5p inhibits glioma migration and invasion by targeting SND1. OncoTargets and therapy 23 30214229
2022 Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1. Journal of translational medicine 22 35739527
2019 LncRNA SND1-IT1 accelerates the proliferation and migration of osteosarcoma via sponging miRNA-665 to upregulate POU2F1. European review for medical and pharmacological sciences 22 31799644
2013 SND1 affects proliferation of hepatocellular carcinoma cell line SMMC-7721 by regulating IGFBP3 expression. Anatomical record (Hoboken, N.J. : 2007) 22 23878061
2012 NF-κB, Sp1 and NF-Y as transcriptional regulators of human SND1 gene. Biochimie 22 23160072
2012 p100 Deficiency is insufficient for full activation of the alternative NF-κB pathway: TNF cooperates with p52-RelB in target gene transcription. PloS one 21 22880094
2022 Mitochondrion-Localized SND1 Promotes Mitophagy and Liver Cancer Progression Through PGAM5. Frontiers in oncology 20 35433434
2020 miR-1224-5p inhibits the proliferation and invasion of ovarian cancer via targeting SND1. Human cell 20 32409958