Affinage

SP100

Nuclear autoantigen Sp-100 · UniProt P23497

Length
879 aa
Mass
100.4 kDa
Annotated
2026-06-10
68 papers in source corpus 32 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP100 is an interferon-inducible nuclear scaffold protein and a core constituent of PML nuclear bodies (ND10) that functions in intrinsic antiviral defense and chromatin-mediated transcriptional regulation (PMID:8810287, PMID:18160441). Its expression is driven by type-I and type-II IFN through an ISRE and GAS element in its promoter (PMID:8810287), and it exists as multiple alternatively spliced isoforms, several carrying SAND, PHD-bromodomain, or HMG chromatin-associated motifs (PMID:9973607, PMID:11313457, PMID:19279115). SP100 is covalently modified by SUMO-1 on a lysine within its HP1-binding region, a modification that confines it to the nucleus and enhances the stability of its complexes with HP1 family heterochromatin proteins; when tethered to DNA, SP100 and its HMG variant act as transcriptional repressors (PMID:9412458, PMID:10212234, PMID:9636146, PMID:11313457). Distinct domains mediate ND10 targeting and homo-oligomerization, allowing SP100 (notably the HMG isoform) to nucleate nuclear body assembly and recruit partners (PMID:11112690). SP100 restricts a broad panel of viruses — HSV-1, HCMV, HPV, EBV, HVS, VZV, and RRV — primarily by repressing viral chromatin transcription, acting independently of and additively with PML, with the SAND-domain isoforms blocking HSV-1 immediate-early promoter activity (PMID:18160441, PMID:19279115, PMID:21734036, PMID:24194542, PMID:28968443, PMID:28439026). Viruses counteract SP100 through SUMO de-modification and proteasome-dependent degradation mediated by viral E3 ubiquitin ligases, including HSV-1 ICP0 acting via the E2 enzyme UbcH5a, VZV ORF61p, and the FGARAT-homolog tegument proteins of HVS (ORF3) and RRV (ORF75) (PMID:10233977, PMID:10023669, PMID:12855769, PMID:20392849, PMID:22278248, PMID:27356898). Beyond viral defense, SP100 is a dose-dependent negative regulator of the ETS1 transcription factor, reducing ETS1 DNA binding and target-gene activation to suppress invasion and angiogenesis (PMID:11909962, PMID:15247905, PMID:15592518), recruits the MRN complex via NBS1 to sequester recombination machinery and suppress alternative lengthening of telomeres (PMID:15767676, PMID:12470659), and acts as a tumor suppressor whose loss triggers senescence escape and genomic instability (PMID:21118961). SP100 is also a substrate of APC/C-Cdc20-mediated proteasomal degradation through a D-box motif (PMID:22086178), and during mitosis its toxic oligomers must be dissolved by SP110 through a direct CARD-CARD interaction to prevent chromosome segregation errors and genotoxic death (PMID:41826696).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Established that SP100 is a bona fide interferon-response gene, defining the regulatory logic by which it is deployed in innate defense.

    Evidence Nuclear run-on, promoter deletion analysis, and EMSA identifying ISRE/GAS elements and IFN factor binding

    PMID:8810287

    Open questions at the time
    • Did not connect IFN induction to a specific downstream antiviral or chromatin function
    • Isoform-specific transcriptional/splicing responses not resolved
  2. 1997 High

    Answered how SP100 subcellular distribution is controlled by showing SUMO-1 conjugation restricts it to the nucleus, linking a post-translational mark to localization.

    Evidence SUMO-1-specific immunoblotting plus cell fractionation and immunofluorescence across cell lines

    PMID:9412458

    Open questions at the time
    • Functional consequence of SUMOylation beyond localization not yet defined
    • SUMO conjugation site not mapped at this stage
  3. 1998 High

    Identified SP100 as a partner of HP1 heterochromatin proteins and a transcriptional repressor, establishing a chromatin-silencing function.

    Evidence Co-IP, colocalization, and promoter-tethering reporter assays; identification of the SP100-HMG splice variant

    PMID:9636146

    Open questions at the time
    • Endogenous genomic targets of repression not identified
    • Direct DNA binding of HMG variant not functionally demonstrated
  4. 1999 High

    Mapped the SP100 domains for SUMOylation, nuclear localization, dimerization and ND targeting and located the SUMO site within the HP1-binding region, suggesting SUMO tunes HP1 interaction.

    Evidence Deletion/point-mutant analysis with localization, dimerization and SUMOylation readouts; splice variant cloning

    PMID:10212234 PMID:9973607

    Open questions at the time
    • Did not directly measure SUMO effect on HP1 binding affinity
    • Functional roles of individual isoforms not assigned
  5. 1999 High

    Revealed that herpesviruses dismantle SP100 by abrogating SUMO modification and triggering proteasomal degradation, defining viral antagonism of ND10 integrity.

    Evidence Immunoblotting of SUMO-modified SP100 and protein levels in HSV-1/CMV-infected cells with MG132 rescue and viral-protein comparison; immuno-EM localization

    PMID:10023669 PMID:10233977 PMID:7493645

    Open questions at the time
    • Viral E3/E2 machinery not yet identified
    • Whether SP100 loss causally enhances viral replication not tested here
  6. 2001 High

    Provided biochemical mechanism for SUMO function by showing SUMOylation stabilizes SP100-HP1 complexes, and expanded the isoform repertoire to chromatin-reader (PHD-bromo) forms.

    Evidence In vitro binding assays comparing SUMOylated vs unmodified SP100; cDNA cloning of SP100C

    PMID:11313457

    Open questions at the time
    • In vitro stabilization not validated for endogenous complexes
    • Chromatin substrates read by the PHD-bromo isoform unknown
  7. 2001 Medium

    Separated the ND10-targeting and self-oligomerization functions of SP100 into distinct domains, clarifying how it docks to and seeds nuclear bodies.

    Evidence GFP-fusion deletion variant transfection and immunofluorescence with/without endogenous SP100

    PMID:11112690

    Open questions at the time
    • Structural basis of oligomerization not resolved
    • Functional importance of oligomerization in vivo not addressed
  8. 2002 High

    Defined a chromatin-independent transcriptional role by showing SP100 binds and dose-dependently inhibits ETS1, repressing invasion-associated gene programs.

    Evidence Yeast two-hybrid, in vitro pulldown, Co-IP, reporter, endogenous gene expression and invasion assays; NBS1 BRCT-mediated SP100 interaction and ectopic POD recruitment

    PMID:11909962 PMID:12470659

    Open questions at the time
    • Mechanism by which SP100 reduces ETS1 DNA binding unresolved
    • Physiological context of NBS1 recruitment not yet linked to a pathway
  9. 2005 High

    Connected SP100 to genome maintenance and angiogenesis control: it sequesters the MRN complex to suppress ALT and antagonizes ETS1-driven endothelial behavior.

    Evidence SP100 overexpression and truncation analysis with telomere length, APB and FISH assays in ALT cells; HUVEC functional assays, microarray and EMSA; EBNA-LP displacement domain mapping

    PMID:15247905 PMID:15592518 PMID:15767676 PMID:16177824

    Open questions at the time
    • Whether endogenous SP100 levels regulate ALT physiologically untested
    • ETS1 target-gene selectivity mechanism unknown
  10. 2007 High

    Demonstrated that SP100 is an independent intrinsic antiviral restriction factor, acting additively with but separately from PML against HSV-1.

    Evidence siRNA single and double knockdown of SP100/PML with quantitative viral gene expression and plaque assays

    PMID:18160441

    Open questions at the time
    • Molecular step of restriction not defined in this study
    • Isoform responsible for restriction not identified
  11. 2009 High

    Pinpointed the SAND-domain isoforms as the active repressors of HSV-1 immediate-early promoters and showed IFN biases splicing toward the inhibitory SP100C isoform.

    Evidence Isoform-selective siRNA, IFN treatment, promoter-luciferase reporters and immunoblotting in infected cells

    PMID:19279115

    Open questions at the time
    • Mechanism by which SAND domain represses viral chromatin not biochemically resolved
    • Splicing regulator directing IFN-induced isoform switch unknown
  12. 2011 High

    Identified two parallel degradation routes for SP100 — viral RING E3 ligases and host APC/C-Cdc20 — defining how its levels are controlled by infection and by the cell-cycle machinery.

    Evidence VZV ORF61p RING mutagenesis and in vitro ligase assays; HCMV IE1 transfection/knockdown with viral titers; Cdc20 overexpression/knockdown and D-box mutant analysis with MG132

    PMID:20392849 PMID:21734036 PMID:22086178

    Open questions at the time
    • Cdc20-mediated degradation does not produce cell-cycle oscillation of SP100, leaving its physiological purpose unclear
    • Direct ubiquitination of SP100 by these ligases not all reconstituted
  13. 2010 High

    Established SP100 as a tumor suppressor whose isoform-specific loss causes senescence escape, genomic instability and tumorigenicity.

    Evidence Isoform-selective shRNA knockdown, nude mouse tumorigenicity, microsatellite and transcriptome analysis with Sp100A rescue

    PMID:21118961

    Open questions at the time
    • Causal chromatin targets driving tumor suppression not defined
    • Relationship between tumor suppression and antiviral repression unresolved
  14. 2013 High

    Extended SP100 restriction to papillomaviruses, showing it limits HPV establishment and that ICP0 N-terminal regions mediate its ND10 dissociation.

    Evidence siRNA depletion in primary keratinocytes with HPV18 immortalization/transcription/replication readouts; ICP0 truncation mapping with localization readouts

    PMID:24089549 PMID:24194542

    Open questions at the time
    • Direct engagement of incoming HPV DNA by SP100 not yet shown at this stage
    • ICP0 domains mapped without identifying degradation cofactors
  15. 2016 High

    Generalized viral antagonism of SP100 across gammaherpesviruses by identifying FGARAT-homolog effectors (HVS ORF3, RRV ORF75) and confirming antiviral roles by knockout.

    Evidence Wild-type vs ORF-deletion virus complementation in SP100-depleted cells; CRISPR-Cas9 knockout; ectopic effector expression and proteasome inhibition

    PMID:22278248 PMID:27356898

    Open questions at the time
    • Biochemical mechanism of FGARAT-homolog-directed SP100 degradation undefined
    • Why RRV degrades SP100 before PML kinetically unexplained
  16. 2017 High

    Resolved the cellular step of restriction by showing SP100 suppresses formation of viral replication compartments and binds viral chromatin directly across the HPV genome.

    Evidence SP100-/- CRISPR cells with replication-compartment counting, viral yields and IFN-beta sensitivity; ChIP of SP100 on HPV chromatin, colocalization and knockdown in differentiating keratinocytes and patient biopsies

    PMID:28439026 PMID:28968443

    Open questions at the time
    • Mechanism of SP100 recruitment to viral chromatin not defined
    • Distinct contributions of SP100 isoforms to chromatin binding unresolved
  17. 2025 High

    Defined a mitotic safety mechanism in which SP110 dissolves toxic SP100 oligomers via direct CARD-CARD interaction to prevent chromosome segregation errors and genotoxicity.

    Evidence Genome-wide CRISPR screen, cryo-EM, AlphaFold modeling, Co-IP, live-cell mitosis imaging and micronucleus/DNA-damage quantification

    PMID:41826696

    Open questions at the time
    • Trigger that converts SP100 into toxic oligomers in mitosis not identified
    • Whether oligomerization links to other SP100 functions (antiviral/chromatin) unknown
  18. 2025 Low

    Proposed an 'inside-out' phase-separation model of nuclear body assembly with SP100-HMG nucleating a liquid core, and assigned Sp100A as the driver of HIRA chaperone recruitment.

    Evidence Live-cell imaging, LLPS assays, cryo-EM/AlphaFold and CRISPR perturbations (preprint); CRISPR Sp100 KO with isoform rescue and IFN stimulation (preprint)

    Open questions at the time
    • Preprints not yet peer-reviewed or independently replicated
    • LLPS-based assembly model not validated against the established SUMO-driven recruitment scheme
    • Functional consequence of HIRA recruitment to PML-NBs not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SP100's chromatin-reader/repressor domains mechanistically silence viral and cellular promoters, and how its multiple functions (antiviral repression, ETS1 regulation, ALT suppression, mitotic oligomer toxicity) are coordinated through a unified molecular activity, remains unresolved.
  • No structural model of SP100 engaging chromatin
  • No defined catalytic or enzymatic activity for SP100 itself
  • Integration of distinct functional outputs by isoform/PTM state not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 2
Localization
GO:0005654 nucleoplasm 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2
Partners
ATRXDAXXETS1HIRAHP1NBS1PMLSP110
Complex memberships
PML nuclear body / ND10

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Sp100 is covalently modified by PIC1/SUMO-1 (SUMO-1) in vivo. Cell fractionation and immunoblotting demonstrated that SUMO-1-modified Sp100 isoforms are exclusively nuclear, whereas non-modified Sp100 is also found in the cytoplasm, indicating that SUMOylation restricts Sp100 to the nucleus. Immunoblotting with SUMO-1-specific monoclonal antibody on cell extracts from stably transfected and untransfected cells; cell fractionation; immunofluorescence colocalization The Journal of cell biology High 9412458
1999 Domains of Sp100 required for SUMOylation, nuclear localization, homodimerization, and ND targeting were mapped. A functional nuclear localization signal is required for SUMOylation, but SUMOylation is not necessary for nuclear import or ND targeting. The specific lysine residue to which SUMO-1 is conjugated was identified and lies within the HP1-binding site, suggesting SUMO modification may modulate HP1 interaction. Deletion and point mutant analysis of Sp100 domains with immunofluorescence and immunoblotting; SUMOylation site mutagenesis The Journal of biological chemistry High 10212234
1998 Sp100 binds directly to members of the heterochromatin protein 1 (HP1) family of non-histone chromosomal proteins. A naturally occurring splice variant, SP100-HMG, contains an HMG-1 domain with potential DNA-binding activity. Both HP1 and SP100-HMG concentrate in PML/SP100 nuclear bodies, and overexpression of SP100 leads to enhanced accumulation of endogenous HP1 in these structures. When tethered to a promoter, SP100, SP100-HMG, and HP1 all behave as transcriptional repressors. Co-immunoprecipitation, immunofluorescence colocalization, transfection-based transcriptional reporter assays in mammalian cells Proceedings of the National Academy of Sciences of the United States of America High 9636146
1999 The HSV-1 ICP0 protein and the CMV IE1 protein specifically abrogate the SUMO-1 modification of PML and Sp100, correlating with complete disruption of nuclear body structure. Adenovirus E4 ORF3, which causes only moderate redistribution of PML, does not affect SUMO-1 modification of Sp100 or PML. These data support a model in which SUMO-1 conjugation is required for structural integrity of nuclear bodies. Immunoblotting for SUMO-modified Sp100 in virus-infected cells; immunofluorescence of nuclear body disruption; comparison across viral proteins Journal of virology High 10233977
1999 HSV-1 infection induces proteasome-dependent degradation of Sp100 protein without altering its mRNA level. The proteasome inhibitor MG132 abrogates HSV-1-induced Sp100 degradation and partially restores NB localization. RanGAP1 (another SUMO-1 conjugate) and PKR are not degraded, indicating specificity. Immunoblotting of Sp100 protein levels in HSV-1-infected cells with/without MG132; RT-PCR for mRNA levels; immunofluorescence Oncogene High 10023669
2003 Degradation of PML and Sp100 by HSV-1 ICP0 is mediated specifically by the E2 ubiquitin-conjugating enzyme UbcH5a. Dominant-negative UbcH5a (C85A) blocked PML and Sp100 degradation and ND10 dispersal, whereas dominant-negative UbcH6 and UbcH7, or wild-type UbcH5a, had no inhibitory effect. ICP0 site 2 (exon 2, RING finger) polyubiquitylates UbcH5a and UbcH6 in vitro. In vitro ubiquitylation assay; ectopic expression of dominant-negative E2 enzymes; immunofluorescence and immunoblotting for PML and Sp100 Proceedings of the National Academy of Sciences of the United States of America High 12855769
2001 SUMO modification of SP100 enhances the stability of SP100-HP1 complexes in vitro. An additional SP100 splice variant, SP100C, was identified containing PHD-bromodomain motifs characteristic of chromatin proteins. TIF1alpha, a chromatin factor homologous to PML and SP100C, is also modified by SUMO-1. In vitro binding assay comparing SUMOylated vs non-SUMOylated SP100 interactions with HP1; cDNA cloning; immunofluorescence Molecular and cellular biology High 11313457
2001 Sp100 contains separate ND10-binding and homo-oligomerization domains. Amino acids 29–152 are sufficient for ND10 targeting and self-aggregation in the absence of endogenous Sp100. The ND10-binding domain and the self-aggregation (homo-oligomerization) domain are separable entities, as demonstrated by fusion of a p53-binding peptide that blocked self-aggregation while retaining ND10 binding. GFP-fusion deletion variant transfection, immunofluorescence localization relative to ND10 markers with and without endogenous Sp100 Journal of cell science Medium 11112690
2002 SP100 physically interacts with the ETS-1 transcription factor both in vitro and in vivo. SP100 negatively modulates ETS-1 transcriptional activation of MMP1 and uPA promoters in a dose-dependent manner, decreases endogenous MMP1 and uPA expression, reduces ETS-1 DNA binding, and inhibits invasion of breast cancer cells. Yeast two-hybrid screen; in vitro pulldown; co-immunoprecipitation; transcriptional reporter assays; endogenous gene expression analysis; invasion assay Molecular and cellular biology High 11909962
2004 SP100 interacts with ETS1 in vitro and in vivo, reduces ETS1 DNA binding, and acts as a dose-dependent inhibitor of ETS1 transcriptional activation. SP100 expression inhibits invasion of breast cancer cells. Yeast two-hybrid; in vitro and in vivo co-immunoprecipitation; EMSA (ETS1 DNA binding); transcriptional reporter assay; Matrigel invasion assay Oncogene High 15247905
2005 SP100 negatively modulates ETS1-dependent angiogenic activity in primary endothelial cells, antagonizing ETS1-mediated network formation, migration, and invasion. Interferon upregulates SP100 in endothelial cells, and microarray analysis revealed SP100 reciprocally regulates a subset of ETS1 target genes including angiogenesis-related factors. HUVEC network formation assay; migration/invasion assays; cDNA microarray; real-time PCR Oncogene Medium 15592518
2005 Overexpression of Sp100 sequesters the MRE11/RAD50/NBS1 (MRN) recombination complex away from ALT-associated PML bodies (APBs), resulting in suppression of the alternative lengthening of telomeres (ALT) mechanism. This caused progressive telomere shortening (~121 bp/population doubling), suppression of rapid telomere length changes, and suppression of APB formation. A C-terminally truncated Sp100 that did not sequester MRN failed to inhibit ALT. Sp100 overexpression in ALT cells; immunofluorescence colocalization; telomere length measurement by Southern blot; FISH; APB quantification; truncation mutant analysis Molecular and cellular biology High 15767676
2002 NBS1 interacts with SP100 via a BRCA carboxyl terminus (BRCT) domain-containing region of NBS1. Co-transfection of PML and SP100 into NT2 cells (lacking endogenous PML/SP100) recruited NBS1 into ectopically formed PODs, indicating SP100 mediates NBS1 recruitment to PML oncogenic domains. Co-immunoprecipitation; immunofluorescence colocalization in normal fibroblasts and ALT cells; ectopic PML/SP100 expression in NT2 cells Biochemical and biophysical research communications Medium 12470659
2005 The EBV EBNA-LP protein interacts with Sp100 and displaces Sp100 and HP1alpha from PML nuclear bodies. This interaction is mediated through conserved region 3 of EBNA-LP and the PML NB-targeting domain of Sp100. Overexpression of Sp100 lacking the PML NB-targeting domain (but not a mutant lacking the HP1alpha interaction domain) was sufficient to coactivate EBNA2 transcription independently of EBNA-LP, indicating Sp100 mediates EBNA-LP coactivation. Co-immunoprecipitation; immunofluorescence; domain deletion mutant analysis; transcriptional reporter assay The EMBO journal High 16177824
2007 Both PML and Sp100 individually restrict ICP0-null HSV-1 replication. Depletion of Sp100 alone from human fibroblasts increases ICP0-null HSV-1 gene expression comparably to PML depletion alone. Simultaneous depletion of both proteins complements the mutant virus to a greater degree than either alone, demonstrating additive/independent antiviral roles. Inhibition of HDAC activity with trichostatin A could not complement ICP0-null virus in normal or PML-depleted cells. siRNA knockdown of PML and/or Sp100; quantitative RT-PCR and immunofluorescence of viral gene expression; plaque assay Journal of virology High 18160441
2009 The three Sp100 isoforms containing a SAND domain (Sp100B, Sp100C, Sp100HMG) block transcription of HSV-1 ICP0 and ICP4 at the promoter level, but IFN-upregulated Sp100 is not degraded by ICP0 (negative result: ICP0 does not hydrolyze any Sp100 isoform). IFN alters differential splicing of Sp100 transcript in favor of the inhibitory Sp100C isoform. All four Sp100 isoforms stabilize ND10 and protect PML from ICP0-mediated degradation. Loss of all Sp100 isoforms reduces PML levels, and vice versa. Isoform-selective siRNA knockdown; IFN treatment; HSV-1 infection; promoter-luciferase reporter assay; immunoblotting; immunofluorescence Journal of virology High 19279115
2010 The RING finger domain of VZV ORF61p has E3 ubiquitin ligase activity essential for autoubiquitination and for dispersion of Sp100-containing nuclear bodies. Disruption of the RING finger (Cys19Gly substitution) abolishes ORF61p-mediated dispersion of Sp100-containing NBs and eliminates E3 ubiquitin ligase activity. Site-directed mutagenesis of RING finger; in vitro ubiquitin ligase assay; immunofluorescence of NB dispersal Journal of virology High 20392849
2011 IE1 of HCMV directly targets Sp100 independently of PML: IE1 expression alone is sufficient to downregulate endogenous Sp100 and abrogates SUMO modification of all Sp100 isoforms. Sp100 knockdown results in more cells initiating HCMV gene expression program. Sp100 is also degraded in a proteasome-dependent manner at late times post-infection, and Sp100 knockdown results in augmented release of progeny virions and increased viral late gene products independently of enhanced IE gene expression. IE1 transfection/cotransfection; siRNA knockdown of Sp100 in HFFs; proteasome inhibitor treatment; immunoblotting; immunofluorescence; viral titer measurement Journal of virology High 21734036
2011 Cdc20, a co-activator of the APC/C, mediates proteasome-dependent degradation of Sp100 via a D-box motif. Overexpression of Cdc20 decreases endogenous Sp100 levels; knockdown of Cdc20 increases Sp100 levels. A D-box deletion mutant of Sp100 is resistant to Cdc20-mediated degradation. Despite being a Cdc20 substrate, Sp100 protein levels do not oscillate through the cell cycle, and overexpression or knockdown of Sp100 has no effect on cell-cycle progression. Cdc20 overexpression and siRNA knockdown; D-box deletion mutant analysis; MG132 proteasome inhibitor treatment; immunoblotting; flow cytometry cell cycle analysis Biochemical and biophysical research communications Medium 22086178
2012 Herpesvirus saimiri (HVS) specifically degrades Sp100 while leaving PML and hDaxx intact. The HVS ORF3 tegument protein (which shares homology with cellular FGARAT) is the viral factor responsible for proteasomal degradation of Sp100. An ORF3-deletion virus is efficiently complemented in Sp100-depleted cells, demonstrating Sp100 restricts HVS in the absence of ORF3. Infection of cells with wild-type and ORF3-deletion HVS; immunoblotting; immunofluorescence; Sp100 knockdown complementation assay; proteasome inhibitor experiments Journal of virology High 22278248
2013 Sp100 depletion in primary human keratinocytes results in substantially increased HPV18 immortalization efficiency, viral transcription, and DNA replication, establishing Sp100 as an intrinsic restriction factor against incoming HPV DNA during the initial establishment phase. siRNA depletion of Sp100 in primary keratinocytes; HPV18 quasivirus/DNA introduction; quantitative immortalization assay; viral transcription and DNA replication measurements mBio High 24194542
2013 Two overlapping regions within the N-terminal half of HSV-1 ICP0 (residues 212–311 for PML degradation/dissociation; residues 212–427 for Sp100 dissociation) promote the dissociation and degradation of PML and dissociation of Sp100 from ND10. Series of ICP0 truncation mutants expressed in human embryonic lung cells; immunofluorescence of PML/Sp100 localization; immunoblotting for PML protein levels Journal of virology Medium 24089549
2015 IFN-κ inhibits HPV31 transcription primarily by inducing Sp100 proteins. RNAi knockdown of Sp100 reversed IFN-κ-mediated inhibition of viral transcription in CIN612-9E cells maintaining extrachromosomal HPV31 genomes. Doxycycline-inducible IFN-κ expression; siRNA knockdown of Sp100; viral transcription measurement; RNA-seq Journal of virology High 26491169
2016 The rhesus monkey rhadinovirus (RRV) FGARAT homolog ORF75 is sufficient to cause proteasomal degradation of SP100 (and subsequently PML). CRISPR-Cas9 knockout of SP100 or PML in target cells increases RRV infection, confirming antiviral roles. RRV targets SP100 for degradation before PML, a distinct kinetic strategy from other gammaherpesviruses. CRISPR-Cas9 knockout of ND10 components; RRV infection of knockout cells; ORF75 expression in transfected/transduced cells; immunoblotting; immunofluorescence; proteasome inhibitor experiments Journal of virology High 27356898
2017 SP100 suppresses HSV replication and assembly of viral replication compartments. In SP100-/- HEp-2 cells, the number of viral replication compartments and wild-type virus yields (at low MOI) are significantly higher than in parental cells. Unlike PML, SP100 loss does not alter sensitivity to IFN-β and SP100-/- cells support replication of ΔICP0 virus. SP100 also enhances PML accumulation. CRISPR/gene-knockout SP100-/- cells; immunofluorescence counting of viral replication compartments; viral yield assays at low MOI; IFN-β sensitivity assay Proceedings of the National Academy of Sciences of the United States of America High 28439026
2017 Sp100 localizes to HPV16 and HPV31 replication foci in primary keratinocytes and in CIN1 cervical biopsies. Sp100 binds across the HPV viral genome (by ChIP), with binding increasing at late stages of infection. siRNA depletion of Sp100 in differentiating HPV31-containing cells increases viral transcription and replication, demonstrating Sp100 represses HPV at late stages of the productive cycle. Immunofluorescence colocalization; ChIP of Sp100 on viral chromatin; siRNA knockdown in differentiating keratinocytes; viral transcription and replication measurements; analysis of patient CIN1 biopsies PLoS pathogens High 28968443
2010 Selective knockdown of Sp100 isoforms in normal human diploid fibroblasts causes rapid cellular senescence followed by emergence of highly tumorigenic Sp100-minus cells that lack ND10/PML bodies, display genomic instability, cytoplasmic p53 sequestration, and activated MYC/RAS/TERT pathways. Re-introduction of Sp100A alone is sufficient to maintain senescence and prevent emergence of tumorigenic cells, identifying Sp100 as a tumor suppressor acting through chromatin-mediated gene regulation. Isoform-selective shRNA knockdown; nude mouse tumorigenicity assay; microsatellite analysis; immunofluorescence; global transcriptome analysis; Sp100A re-expression rescue Cancer research High 21118961
2011 Sp100 interacts with phage ΦC31 integrase and inhibits ΦC31 integrase-mediated recombination. The interaction maps to residues 81-84 (RILN) of ΦC31 integrase. Knockdown of endogenous Sp100 increases ΦC31 integrase-mediated recombination without affecting reporter gene expression. Yeast two-hybrid screen; co-immunoprecipitation; peptide array hybridization; siRNA knockdown with recombination reporter assay Acta biochimica Polonica Medium 21383994
1999 Sp100 and PML are sequestered in viral translucent patches (finely granular material at the nuclear border) during prolonged HSV-1 infection, as visualized by immunoelectron microscopy. Both proteins are components not only of nuclear bodies but also of interchromatin granule-associated zones in uninfected cells, suggesting a role in splicing events. Immunoelectron microscopy of ultrathin sections of HSV-1-infected HeLa cells Experimental cell research Medium 7493645
1999 Sp100 splice variants were identified: one class contains an HMG-box domain (SP100-HMG) and another contains an HNPP-box domain related to interferon-inducible nuclear phosphoproteins. When transiently expressed, both classes of variants localize in part to nuclear dots/PML bodies and additionally to other nuclear domains distinct from full-length Sp100. cDNA cloning; Sp100 gene 3'-end analysis; transient transfection with immunofluorescence localization Journal of cell science Medium 9973607
1996 IFN-beta induces rapid, protein-synthesis-independent transcriptional upregulation of both Sp100 and PML genes. Nuclear run-on analysis revealed synergistic activation by type-I and type-II IFNs. The Sp100 promoter contains an imperfect IFN-stimulated response element (ISRE) and an IFN-gamma activation site (GAS), with the ISRE binding ISGF2 strongly and ISGF3 weakly. Nuclear run-on transcription assay; promoter cloning and functional analysis; transient transfection reporter assay; electrophoretic mobility shift assay (EMSA) with IFN-induced factors The Journal of biological chemistry High 8810287
2025 Sp100-HMG autonomously nucleates into liquid-like condensates via its multimerization domain and intrinsically disordered region (IDR), initiating an 'inside-out' assembly of PML nuclear bodies. Sp100-HMG forms a liquid core that recruits PML (via SUMOylation-directed recruitment) and client proteins DAXX and ATRX. This hierarchical assembly is required for proper transcriptional programs and cell-cycle dynamics in HEp-2 cells. Live-cell imaging of condensate formation; cryo-EM and AlphaFold modeling (from paper 65 cross-reference); LLPS assays; domain mutant analysis; CRISPR-based perturbations; transcriptome analysis bioRxivpreprint Low
2025 SP110 directly interacts with SP100 via their CARD domains and dissolves toxic SP100 oligomers. Loss of SP110 leads to mitotic retention of SP100 and PML bodies, which associate with and perturb segregating chromosomes, causing micronucleus formation, DNA damage, and genotoxic cell death. SP100 oligomers are thus toxic during mitosis unless dissolved by SP110. Genome-wide CRISPR screen; cryo-electron microscopy; AlphaFold modeling; co-immunoprecipitation; live-cell imaging of mitosis; micronucleus quantification; DNA damage markers Nature cell biology High 41826696
2025 Sp100A isoform is the primary driver of HIRA histone chaperone localization to PML nuclear bodies. In Sp100 CRISPR knockout keratinocytes, HIRA and its complex members UBN1 and ASF1a fail to localize to PML-NBs even after IFN stimulation. The SUMO-interacting motif (SIM) of Sp100A plays an important role in this function. Sp100 KO does not affect keratinocyte differentiation or PML-NB formation itself. CRISPR-Cas9 Sp100 knockout; exogenous expression of individual Sp100 isoforms; immunofluorescence colocalization; IFN stimulation bioRxivpreprint Medium

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. The Journal of cell biology 285 9412458
1999 Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 281 10023669
1999 Viral immediate-early proteins abrogate the modification by SUMO-1 of PML and Sp100 proteins, correlating with nuclear body disruption. Journal of virology 258 10233977
1998 Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proceedings of the National Academy of Sciences of the United States of America 240 9636146
1999 The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers. The Journal of biological chemistry 228 10212234
2007 Replication of ICP0-null mutant herpes simplex virus type 1 is restricted by both PML and Sp100. Journal of virology 185 18160441
1992 IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. Journal of immunology (Baltimore, Md. : 1950) 150 1281200
2000 Sp110 localizes to the PML-Sp100 nuclear body and may function as a nuclear hormone receptor transcriptional coactivator. Molecular and cellular biology 125 10913195
2003 The degradation of promyelocytic leukemia and Sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme UbcH5a. Proceedings of the National Academy of Sciences of the United States of America 117 12855769
2005 Suppression of alternative lengthening of telomeres by Sp100-mediated sequestration of the MRE11/RAD50/NBS1 complex. Molecular and cellular biology 114 15767676
1995 Two nuclear dot-associated proteins, PML and Sp100, are often co-autoimmunogenic in patients with primary biliary cirrhosis. Scandinavian journal of immunology 109 7631159
2001 Common properties of nuclear body protein SP100 and TIF1alpha chromatin factor: role of SUMO modification. Molecular and cellular biology 108 11313457
1996 Interferon-modulated expression of genes encoding the nuclear-dot-associated proteins Sp100 and promyelocytic leukemia protein (PML). European journal of biochemistry 106 8681971
1987 Autoimmune sera recognize a 100 kD nuclear protein antigen (sp-100). Clinical and experimental immunology 106 3308206
2005 Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100. The EMBO journal 80 16177824
1997 Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatology (Baltimore, Md.) 77 9362351
2013 Sp100 provides intrinsic immunity against human papillomavirus infection. mBio 74 24194542
1996 The interferon (IFN)-stimulated gene Sp100 promoter contains an IFN-gamma activation site and an imperfect IFN-stimulated response element which mediate type I IFN inducibility. The Journal of biological chemistry 70 8810287
2022 A novel long noncoding RNA SP100-AS1 induces radioresistance of colorectal cancer via sponging miR-622 and stabilizing ATG3. Cell death and differentiation 66 35978049
2002 Sp100 interacts with ETS-1 and stimulates its transcriptional activity. Molecular and cellular biology 61 11909962
2015 Contribution of the Major ND10 Proteins PML, hDaxx and Sp100 to the Regulation of Human Cytomegalovirus Latency and Lytic Replication in the Monocytic Cell Line THP-1. Viruses 59 26057166
1992 Autoantibodies to the nuclear Sp100 protein in primary biliary cirrhosis and associated diseases: epitope specificity and immunoglobulin class distribution. Scandinavian journal of immunology 59 1384113
2011 Evidence for a dual antiviral role of the major nuclear domain 10 component Sp100 during the immediate-early and late phases of the human cytomegalovirus replication cycle. Journal of virology 52 21734036
2003 Association between the primary biliary cirrhosis specific anti-sp100 antibodies and recurrent urinary tract infection. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 50 14674671
1999 Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. Journal of cell science 50 9973607
2002 Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders. Clinical and experimental immunology 45 11882049
2009 Differential functions of interferon-upregulated Sp100 isoforms: herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. Journal of virology 44 19279115
2015 Interferon Kappa Inhibits Human Papillomavirus 31 Transcription by Inducing Sp100 Proteins. Journal of virology 43 26491169
2005 SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene 42 15592518
2004 SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene 41 15247905
2001 Evidence for separate ND10-binding and homo-oligomerization domains of Sp100. Journal of cell science 41 11112690
2012 Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis. Clinica chimica acta; international journal of clinical chemistry 38 22503841
2012 Herpesvirus saimiri antagonizes nuclear domain 10-instituted intrinsic immunity via an ORF3-mediated selective degradation of cellular protein Sp100. Journal of virology 35 22278248
1998 The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis. Journal of hepatology 34 9625318
2010 The RING finger domain of Varicella-Zoster virus ORF61p has E3 ubiquitin ligase activity that is essential for efficient autoubiquitination and dispersion of Sp100-containing nuclear bodies. Journal of virology 31 20392849
2017 Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle. PLoS pathogens 30 28968443
2017 The SP100 component of ND10 enhances accumulation of PML and suppresses replication and the assembly of HSV replication compartments. Proceedings of the National Academy of Sciences of the United States of America 28 28439026
2003 Clinical significance of anti-multiple nuclear dots/Sp100 autoantibodies. Scandinavian journal of gastroenterology 28 14531539
1999 Identification of major linear epitopes on the sp100 nuclear PBC autoantigen by the gene-fragment phage-display technology. Autoimmunity 27 10052683
2015 SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis. Journal of immunology research 26 26347895
2000 Back to the roots of a new exon--the molecular archaeology of a SP100 splice variant. Genomics 26 10766566
1995 Sequestration of PML and Sp100 proteins in an intranuclear viral structure during herpes simplex virus type 1 infection. Experimental cell research 26 7493645
2002 Recruitment of NBS1 into PML oncogenic domains via interaction with SP100 protein. Biochemical and biophysical research communications 23 12470659
1996 A highly amplified mouse gene is homologous to the human interferon-responsive Sp100 gene encoding an autoantigen associated with nuclear dots. Molecular and cellular biology 23 8622659
2021 The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection. Frontiers in cellular and infection microbiology 18 33598438
2011 SP100 reduces malignancy of human glioma cells. International journal of oncology 17 21274506
1998 Evolution by fusion and amplification: the murine Sp100-rs gene cluster. Cytogenetics and cell genetics 17 9678363
1999 Deletion of the fiber gene induces the storage of hexon and penton base proteins in PML/Sp100-containing inclusions during adenovirus infection. Biology of the cell 16 10629941
1995 A member of the mouse LRR transcript family with homology to the human Sp100 gene. Hereditas 16 8537240
2016 Viral FGARAT Homolog ORF75 of Rhesus Monkey Rhadinovirus Effects Proteasomal Degradation of the ND10 Components SP100 and PML. Journal of virology 15 27356898
2013 Two overlapping regions within the N-terminal half of the herpes simplex virus 1 E3 ubiquitin ligase ICP0 facilitate the degradation and dissociation of PML and dissociation of Sp100 from ND10. Journal of virology 15 24089549
1997 Structure and expression of the murine Sp100 nuclear dot gene. Genomics 13 9268632
2010 Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Cancer research 12 21118961
2013 Detection of anti-SP100 antibodies in primary biliary cirrhosis. Comparison of ELISA and immunofluorescence. Journal of immunoassay & immunochemistry 11 23859785
2011 Cdc20 mediates D-box-dependent degradation of Sp100. Biochemical and biophysical research communications 11 22086178
2019 Expression of Sp100 Protein in Human Papillomavirus-Associated Sinonasal Inverted Papilloma. Ear, nose, & throat journal 8 31272209
2007 Comparison of two ELISA assays for anti-Sp100 determination. Annals of the New York Academy of Sciences 8 17785307
2010 Low expression of Sp100 in laryngeal cancer: correlation with cell differentiation. Medical science monitor : international medical journal of experimental and clinical research 7 20512085
2023 A Novel Fusion Partner, SP100, Drives Nuclear Dot Localization of ALK in Epithelioid Fibrous Histiocytoma. The American Journal of dermatopathology 4 37377191
2021 Clinical impact of antibodies to Sp100 on a bacterial infection in patients with primary biliary cholangitis. Journal of clinical laboratory analysis 3 34623692
2018 The contribution of SP100 to cottontail rabbit papillomavirus transcription and replication. The Journal of general virology 3 29458675
2011 Sp100 interacts with phage ΦC31 integrase to inhibit its recombination activity. Acta biochimica Polonica 2 21383994
2026 An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity. Nature cell biology 1 41826696
2025 Clinical and mechanistic insights into the expression of SP100 family proteins in various cancers: a systematic review. BMC cancer 1 41188771
2013 [Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 24025137
2012 Role and fate of SP100 protein in response to Rep-dependent nonviral integration system. Applied microbiology and biotechnology 1 22419217
2025 Evaluating the diagnostic efficacy of anti-M2-3E, anti-gp210, and anti-sp100 antibodies in primary biliary cirrhosis. Laboratory medicine 0 40973111
2001 Molecular archeology of an SP100 splice variant revisited: dating the retrotranscription and Alu insertion events. Genome biology 0 11574059

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