Affinage

SUN2

SUN domain-containing protein 2 · UniProt Q9UH99

Length
717 aa
Mass
80.3 kDa
Annotated
2026-04-28
41 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUN2 is an inner nuclear membrane protein that functions as a core structural component of the LINC complex, coupling the nucleoskeleton to the cytoskeleton to transduce mechanical and biochemical signals between the nucleus and the cell exterior. Its C-terminal SUN domain resides in the perinuclear lumen where it undergoes Ca²⁺- and disulfide-regulated trimerization to engage KASH-domain nesprins, while INM targeting requires a classical NLS, a Golgi-retrieval signal, and the SUN domain itself; protein levels are controlled by CK2/CTDNEP1-regulated SCFβTrCP ubiquitination followed by p97-dependent membrane extraction (PMID:15082709, PMID:20551905, PMID:29995584, PMID:37188462, PMID:36318477). Through this nucleocytoskeletal linkage, SUN2 mediates myonuclear positioning, meiotic telomere tethering, DNA damage response signaling via interaction with DNA-PK, mechanotransduction of ECM stiffness to regulate mitotic spindle organization and chromatin state (including EZH2-dependent histone methylation), calcium-triggered nuclear actin polymerization via association with the formin INF2, and stiffness-dependent fibrotic gene expression (PMID:19509342, PMID:17452644, PMID:22863315, PMID:36322767, PMID:39317734, PMID:41890082). SUN2 also participates in viral biology: it maintains HIV-1 latency by tethering repressive chromatin at the proviral LTR via lamin A/C, facilitates flavivirus replication organelle formation through cytoskeletal rearrangement, and restricts HSV-1 egress by regulating perinuclear space width (PMID:29717016, PMID:38177122, PMID:35435724).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Establishing that SUN2 is an inner nuclear membrane protein with its SUN domain in the perinuclear lumen resolved the basic topology and subcellular localization of this previously uncharacterized protein.

    Evidence Immunofluorescence, EM, subcellular fractionation, and GFP-tagged truncation mapping in HeLa cells

    PMID:15082709

    Open questions at the time
    • No binding partners identified
    • Functional role unknown
    • Mechanism of INM retention not defined
  2. 2007 High

    Demonstrating SUN2 localization at meiotic telomere attachment sites established its first specialized biological function — tethering telomeres to the nuclear envelope during meiosis for bouquet formation.

    Evidence Immunolocalization and EM in mouse spermatocytes

    PMID:17452644

    Open questions at the time
    • Loss-of-function meiotic phenotype not yet shown
    • Mechanism of telomere recognition not defined
  3. 2009 High

    Genetic epistasis in Sun1/Sun2 double-knockout mice revealed that SUN proteins are collectively required to retain Nesprin-1 at the nuclear envelope and position myonuclei, establishing the LINC complex as essential for nuclear-cytoskeletal coupling in muscle.

    Evidence Sun1⁻/⁻, Sun2⁻/⁻, and double-KO mice with histology and IF

    PMID:19509342

    Open questions at the time
    • Individual contribution of SUN2 vs SUN1 not fully separated
    • Molecular basis of force transmission not resolved
  4. 2010 High

    Systematic mutagenesis revealed that INM targeting of SUN2 requires three cooperating signals — a classical NLS, an arginine-based Golgi retrieval motif, and the lumenal SUN domain — explaining how the protein navigates the secretory pathway to reach the inner nuclear membrane.

    Evidence Deletion/mutation analysis with fluorescence localization in human cells

    PMID:20551905

    Open questions at the time
    • Identity of Golgi retrieval receptor/coatomer interaction not fully characterized
    • Kinetics of INM targeting not measured
  5. 2012 High

    Two concurrent advances linked SUN2 to genome integrity: interaction with DNA-PK and a requirement for ATM/γH2AX activation in double-KO MEFs established SUN proteins as components of the DNA damage response, while studies in laminopathy cells showed SUN2 organization depends on prelamin A farnesylation status.

    Evidence Co-IP screen, Sun1/2 double-KO MEFs with DDR readouts; IF and pharmacological rescue in MADA patient fibroblasts

    PMID:22706480 PMID:22863315

    Open questions at the time
    • Whether SUN2 directly contacts DNA-PK or acts through lamin scaffolding unknown
    • Mechanism by which prelamin A farnesylation disrupts SUN2 lattice not defined at structural level
  6. 2014 High

    Disease-associated SUN1/SUN2 variants impaired nuclear repositioning and microtubule nucleation at the nuclear envelope, providing the first human-genetics evidence that LINC complex dysfunction contributes to muscle disease pathogenesis.

    Evidence Nuclear repositioning assays in patient fibroblasts and myotubes expressing SUN variants

    PMID:25210889

    Open questions at the time
    • Precise structural basis of variant pathogenicity not resolved
    • Whether SUN2 variants alone are sufficient to cause disease unclear
  7. 2016 High

    Multiple studies converged on a role for SUN2 in early HIV-1 infection, showing that overexpressed SUN2 blocks HIV nuclear import in a capsid- and CypA-dependent manner, while endogenous SUN2 in primary T cells supports wild-type HIV reverse transcription and nuclear entry.

    Evidence Overexpression/knockdown, CypA perturbation, viral passaging, infection assays in cell lines and primary CD4⁺ T cells

    PMID:26865710 PMID:27149839

    Open questions at the time
    • Contradictory gain-of-function vs loss-of-function outcomes not fully reconciled
    • Direct physical interaction with capsid in cells not demonstrated
  8. 2017 High

    Further work clarified that SUN2 silencing in primary T cells reduces HIV infection indirectly by impairing T cell activation and proliferation, while in vitro capsid-nanotube pulldowns confirmed a direct SUN2-capsid physical interaction, partially resolving the apparent contradictions.

    Evidence siRNA knockdown with activation/proliferation assays in primary T cells; capsid-nucleocapsid nanotube pulldown plus CRISPR KO

    PMID:28077629 PMID:28747499

    Open questions at the time
    • Whether the capsid interaction is physiologically relevant during natural infection remains debated
    • In vivo HIV infection in SUN2 KO model not tested
  9. 2018 High

    ChIP experiments revealed that SUN2, together with lamin A/C, tethers repressive nucleosomes at the HIV-1 5ʹ-LTR to maintain proviral latency, establishing a chromatin-level mechanism for SUN2's impact on HIV gene expression distinct from its nuclear import role.

    Evidence Co-IP, ChIP, siRNA knockdown with TNF-α reactivation in latently infected cell lines

    PMID:29717016

    Open questions at the time
    • Whether this latency mechanism operates in primary reservoir cells in vivo unknown
    • How SUN2 is recruited specifically to the LTR not defined
  10. 2018 Medium

    Biochemical and computational analysis showed that full-length SUN2 exists as an autoinhibited monomer that undergoes Ca²⁺-driven trimerization via coiled-coil domains CC1/CC2, a prerequisite for KASH engagement — revealing an activation switch for LINC complex assembly.

    Evidence Molecular dynamics simulation, gel filtration, E452 mutagenesis

    PMID:29995584

    Open questions at the time
    • No crystal structure of full-length SUN2 trimer
    • In vivo Ca²⁺ regulation of trimerization not demonstrated
    • Autoinhibition mechanism not validated by structural biology
  11. 2019 High

    SUN2-null mice developed cardiac hypertrophy with enhanced AKT/MAPK signaling but without fibrosis due to elevated MAN1 that suppresses TGFβ, demonstrating that SUN2 modulates the coupling between hypertrophic and fibrotic signaling at the nuclear lamina.

    Evidence SUN2 KO mice with cardiac histology, western blots for AKT/MAPK/TGFβ/MAN1

    PMID:31091167

    Open questions at the time
    • Whether SUN2 directly regulates MAN1 levels or indirectly through NE reorganization is unknown
    • Heart-specific conditional KO not performed
  12. 2021 Medium

    Mass spectrometry identified SUN2 as an interactor of spliceosome components (SNRPD2, SNRPD3, NHP2L1), and SUN2 depletion caused sororin intron retention, linking SUN2 to pre-mRNA splicing regulation and consequently to sister chromatid cohesion.

    Evidence Pulldown/MS, RT-PCR for splicing, FACS in TNBC cell lines

    PMID:33648524

    Open questions at the time
    • Whether SUN2 is a stable spliceosome component or an indirect regulator unclear
    • Not replicated in non-cancer cell types
    • Mechanism of SUN2 action on splicing not reconstituted
  13. 2022 High

    A complete degradation pathway was reconstituted: CK2 phosphorylates SUN2 to create a degron recognized by SCFβTrCP, leading to ubiquitination and p97-dependent membrane extraction for proteasomal degradation, with CTDNEP1 opposing CK2 — establishing how SUN2 abundance is dynamically controlled and why its dysregulation causes nuclear architecture defects and chromosome missegregation.

    Evidence Co-IP, in vivo/in vitro ubiquitination, phosphorylation assays, p97/proteasome inhibition, CRISPR/siRNA, live-cell imaging of chromosome segregation

    PMID:36318477

    Open questions at the time
    • Cell-cycle timing of CK2/CTDNEP1 regulation not mapped
    • Whether this pathway is tissue-specific is unknown
  14. 2022 High

    Two parallel discoveries linked SUN2 to mechanotransduction and viral defense: ECM stiffness upregulates SUN2 to organize astral microtubules during mitosis, and SUN2 restricts HSV-1 egress by maintaining perinuclear space width.

    Evidence Variable-stiffness gels with live mitotic imaging and SUN2 perturbation; dominant-negative constructs and RNAi with HSV-1 yield and EM of perinuclear spacing

    PMID:35435724 PMID:36322767

    Open questions at the time
    • How ECM stiffness transcriptionally upregulates SUN2 is not defined
    • Whether SUN2's perinuclear spacing role is relevant for HSV-1 in vivo unknown
  15. 2023 High

    Multiple 2023 studies revealed that SUN2 functions as a biophysical sensor: its lumenal disulfide bonds undergo KASH-dependent redox rearrangements essential for LINC assembly and cell migration; SUN2 clustering transduces progerin aggregation into ER stress in HGPS; and SUN2 levels regulate nuclear stiffness and mechanically-induced DNA damage via RhoA/F-actin.

    Evidence Disulfide trapping and conformation-specific antibody with migration assays; siRNA of SUN2 with ER stress reporters in HGPS cells; siRNA with nuclear deformability/γH2AX in MSCs under cyclic stretch

    PMID:37188462 PMID:37198162 PMID:37210724

    Open questions at the time
    • Identity of ER oxidoreductase controlling SUN2 redox state unknown
    • Mechanism of SUN2 clustering-to-ER stress signal transduction not reconstituted
    • Whether reducing SUN2 is therapeutically viable in HGPS untested
  16. 2024 High

    SUN2 was shown to promote flavivirus replication by facilitating cytoskeletal rearrangement and replication organelle formation through actin–NS1 interaction, and independently to mediate calcium-triggered nuclear actin polymerization via the formin INF2 — revealing LINC-independent nuclear functions.

    Evidence CRISPR KO with co-IP (actin–NS1) and in vivo ZIKV model; siRNA with live nuclear actin imaging, co-IP of SUN2–INF2, calcium manipulation

    PMID:38177122 PMID:39317734

    Open questions at the time
    • How SUN2 recruits INF2 specifically at the nuclear envelope not structurally resolved
    • Whether SUN2–INF2 function is relevant for endogenous nuclear actin beyond calcium signaling unknown
  17. 2026 High

    Recent work expanded SUN2's mechanotransduction role to fibrosis and drug response: SUN2 mediates stiffness-dependent ECM gene induction and EZH2-regulated chromatin remodeling in fibrosis, transmits paclitaxel-induced microtubule forces to cause lamin A/C polyubiquitylation and nuclear damage, and farnesylated prelamin A impairs LINC complex function by reducing SUN2/nesprin-2 mobility.

    Evidence Sun2 KO mice in bleomycin lung and skin fibrosis models with chromatin/transcription analysis; cryo-ET plus ubiquitylation assays with SUN2 KO in paclitaxel-treated cells; FRAP and polarity assays with farnesylation mutants

    PMID:41367359 PMID:41889916 PMID:41890082 PMID:42011117

    Open questions at the time
    • Whether SUN2-dependent fibrotic mechanism is shared across all organ fibroses unknown
    • The ubiquitin ligase mediating SUN2-dependent lamin A/C degradation during paclitaxel treatment not identified
    • Therapeutic potential of targeting SUN2 in fibrosis or chemoresistance untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of full-length SUN2 autoinhibition and trimerization, how ECM stiffness signals are transduced to SUN2 transcriptional upregulation, the identity of ER oxidoreductases controlling SUN2 disulfide switches, and whether tissue-specific SUN2 functions can be therapeutically targeted in fibrosis, laminopathies, or viral infection.
  • No full-length SUN2 structure available
  • Upstream mechanotransduction pathway to SUN2 expression undefined
  • In vivo therapeutic targeting not explored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0008092 cytoskeletal protein binding 4 GO:0140299 molecular sensor activity 4
Localization
GO:0005635 nuclear envelope 5 GO:0005634 nucleus 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 1 R-HSA-73894 DNA Repair 1 R-HSA-8953854 Metabolism of RNA 1
Partners
BTRCCSNK2A1DNA-PKCSINF2LMNASUN1SYNE1SYNE2
Complex memberships
LINC complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SUN2 is a mammalian inner nuclear membrane (INM) protein; its N-terminal region (amino acids 26–339) is sufficient for nuclear envelope localization, while its C-terminal SUN domain resides in the perinuclear lumen between the inner and outer nuclear membranes. Immunofluorescence, subcellular fractionation, EM, recombinant GFP/V5-tagged protein expression in HeLa cells The Journal of biological chemistry High 15082709
2007 SUN2 specifically localizes to meiotic telomere attachment sites at the nuclear envelope and is part of a membrane-spanning fibrillar complex that interconnects telomeres with cytoplasmic structures, functioning in meiotic telomere tethering and bouquet formation. Immunolocalization, electron microscopy, co-localization analysis in mouse spermatocytes Proceedings of the National Academy of Sciences of the United States of America High 17452644
2009 SUN1 and SUN2 act together at the nuclear envelope to retain Syne-1/Nesprin-1 at the nuclear envelope of muscle cells; loss of both proteins (Sun1/2 double-knockout) displaces Syne-1 from the NE and disrupts both synaptic and non-synaptic myonuclear positioning in skeletal muscle. Genetic knockout (Sun1-/-, Sun2-/-, double-KO mice), immunofluorescence, histology Proceedings of the National Academy of Sciences of the United States of America High 19509342
2010 INM targeting of SUN2 requires three distinct elements: a classical nuclear localization signal (cNLS) in the nucleoplasmic N-terminal domain, a cluster of arginines that mediates Golgi retrieval via coatomer, and the C-terminal lumenal SUN domain. Deletion/mutation analysis, fluorescence microscopy, Golgi retrieval assays in human cells The EMBO journal High 20551905
2011 Lamin A (but not lamin C) is required to maintain SUN2 at the nuclear envelope; Rab5 overexpression redistributes SUN2 to endosomes via its SUN domain, and SUN2 participates in endocytosis, as its overexpression stimulates transferrin uptake while knockdown attenuates it. siRNA knockdown, overexpression of Rab5 mutants, co-localization, transferrin uptake assay in HeLa and lamin A/C-deficient cells PloS one Medium 21655223
2012 SUN1 and SUN2 interact with the DNA-PK complex (which functions in non-homologous end joining) and are required for proper activation of ATM and H2AX after DNA damage; Sun1/Sun2 double-KO MEFs show premature proliferation arrest, increased apoptosis, DNA damage, and impaired DDR signaling. Biochemical co-immunoprecipitation screen, Sun1/2 double-KO MEFs, flow cytometry, immunofluorescence for γH2AX and pATM Current biology : CB High 22863315
2012 In mandibuloacral dysplasia (MADA) cells, farnesylated prelamin A accumulation alters SUN2 distribution at the nuclear envelope (forming a disorganized lattice); statin treatment partially rescues proper SUN2 organization, indicating SUN2 localization depends on prelamin A farnesylation status. Immunofluorescence, pharmacological treatment (farnesyltransferase inhibitors, statins) in MADA patient fibroblasts Histochemistry and cell biology Medium 22706480
2014 Disease-associated SUN1 and SUN2 variants impair rearward nuclear repositioning in fibroblasts (defective nuclear-cytoskeletal coupling), and patient myotubes with compound heterozygous SUN1 mutations show loss of pericentrin recruitment to the NE, impaired microtubule nucleation at the NE, and defective myonuclear positioning. Nuclear repositioning assay in fibroblasts, immunofluorescence in patient myotubes and C2C12 myotubes expressing SUN variants PLoS genetics High 25210889
2016 SUN2 overexpression blocks HIV-1 infection between reverse transcription and nuclear import in a capsid-dependent, cyclophilin A (CypA)-dependent manner; this block and the accompanying nuclear shape deformation both map to the nucleoplasmic domain of SUN2 that interacts with the nuclear lamina. Passaging selected a single CA mutation conferring SUN2 resistance. Overexpression, siRNA knockdown, CypA inhibition, chimeric virus analysis, capsid passaging in cell lines and primary monocyte-derived dendritic cells Journal of virology High 26865710
2016 Endogenous SUN2 in primary CD4+ T cells is required for the positive effects of CypA on HIV reverse transcription and nuclear import; SUN2 and CypA act in the same pathway to promote wild-type HIV infection, whereas capsid mutants restricted by CypA are blocked at nuclear import in a SUN2-dependent manner. siRNA knockdown of SUN2, CypA inhibition/knockdown, infection assays with HIV-1, HIV-2, SIVmac capsid mutants in primary CD4+ T cells Cell reports High 27149839
2017 SUN2 silencing in primary CD4+ T cells reduces HIV infection indirectly by impairing T cell activation and proliferation (reduced activation markers, viability, and viral protein expression), rather than through a direct CypA-dependent antiviral mechanism. siRNA knockdown, flow cytometry for activation markers, proliferation and viability assays, infection assays in primary CD4+ T cells Journal of virology High 28077629
2017 SUN1 and SUN2 overexpression inhibit nuclear import of HIV-1 cDNA; in vitro-assembled HIV-1 capsid-nucleocapsid nanotubes capture SUN1 and SUN2 from cell lysates, indicating direct interaction with the viral capsid. CRISPR/Cas9 knockout of SUN2 modestly reduces HIV-1 infectivity. Overexpression screen, CRISPR/Cas9 knockout, capsid-nucleocapsid nanotube pulldown from cell lysates, infection assays Journal of virology High 28747499
2018 SUN2 associates with lamin A/C to tether repressive nucleosomes 1 and 2 at the HIV-1 5'-LTR, blocking RNA polymerase II recruitment; SUN2 knockdown converts this chromatin to an active state, enhancing RNA Pol II phosphorylation and recruitment to the LTR, leading to HIV-1 reactivation from latency. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown, TNF-α reactivation assay in HIV-latently infected cell lines mBio High 29717016
2018 Full-length SUN2 must transition from an autoinhibited monomer to a trimer (mediated by coiled-coil domains CC1 and CC2 preceding the SUN domain) to bind KASH; MD simulations and gel filtration identify residue E452 on CC1 as important for monomer-trimer transition, and Ca2+ can drive this transition. Molecular dynamics simulation (~1 µs), gel filtration chromatography, mutagenesis of E452 Molecular biology of the cell Medium 29995584
2019 SUN2-null mice develop cardiac hypertrophy with enhanced AKT/MAPK signaling but without fibrosis; in the absence of SUN2, levels of MAN1 (a negative regulator of TGFβ signaling) are elevated at the nuclear envelope, uncoupling hypertrophy from profibrotic TGFβ signaling. SUN2 knockout mouse model, cardiac histology, western blot for AKT/MAPK/TGFβ pathway components and MAN1 Molecular biology of the cell High 31091167
2021 SUN2 is a component of a spliceosome complex; pulldown followed by mass spectrometry identified SUN2 as interacting with splicing factors SNRPD2, SNRPD3, and NHP2L1, and SUN2 is required for efficient sororin pre-mRNA splicing, thereby regulating sister chromatid cohesion and cell proliferation. RNAi screen, pulldown/mass spectrometry, RT-PCR for sororin intron retention, FACS, molecular imaging in TNBC cell lines Journal of experimental & clinical cancer research : CR Medium 33648524
2022 Casein Kinase 2 phosphorylates SUN2, enabling its binding to the SCFβTrCP ubiquitin ligase; SCFβTrCP ubiquitinates SUN2, which is then extracted from the membrane by p97 AAA ATPase and degraded by the proteasome. CTDNEP1 phosphatase opposes CK2 to stabilize SUN2. Non-degradable SUN2 accumulation causes aberrant nuclear architecture, DNA damage vulnerability, and increased lagging chromosomes. Co-immunoprecipitation, ubiquitination assays, phosphorylation assays, p97 inhibition, proteasome inhibition, CRISPR/siRNA knockdown, live-cell imaging, chromosome segregation analysis eLife High 36318477
2022 SUN2 is required for HSV-1 restriction: disruption of SUN2 (by dominant-negative constructs or RNAi) increases extracellular HSV-1 viral yields, and SUN2 has greater impact on perinuclear spacing in infected cells than SUN1, suggesting SUN2 restricts HSV-1 egress by regulating perinuclear space width. Dominant-negative SUN constructs, RNAi knockdown, viral yield assays, electron microscopy for perinuclear spacing Journal of virology Medium 35435724
2022 ECM rigidity upregulates SUN2 expression, which promotes metaphase-to-anaphase transition by organizing astral microtubules during mitosis; on soft ECM, low SUN2 levels perturb astral microtubule organization and delay anaphase onset. Polyacrylamide gels of varying stiffness, SUN2 knockdown/overexpression, live-cell imaging of mitosis, immunofluorescence of mitotic spindle Proceedings of the National Academy of Sciences of the United States of America High 36322767
2023 Conserved cysteine residues in SUN2 undergo KASH-dependent inter- and intra-molecular disulfide bond rearrangements in the ER lumen; disruption of the terminal SUN2 disulfide bond impairs SUN2 localization, turnover, LINC complex assembly, cytoskeletal organization, and cell migration. ER lumenal components regulate SUN2 cysteine redox state. Conformation-specific antibody, biochemical disulfide trapping, KASH co-expression experiments, pharmacological and genetic ER redox perturbations, cell migration assays Life science alliance High 37188462
2023 Progerin aggregation at the nuclear envelope triggers ER stress in HGPS in a SUN2-dependent manner; SUN2 clustering in the nuclear membrane is required for ER stress induction, suggesting SUN2 acts as a sensor that signals nuclear protein aggregates to the ER lumen. siRNA knockdown of SUN2, ER stress reporters, immunofluorescence of SUN2 clustering in HGPS cells Cell reports Medium 37210724
2023 Sun2 suppression reduces nuclear stiffness by increasing nuclear decoupling and deformability, thereby diminishing mechanical stress-induced nuclear/DNA damage in mesenchymal stromal cells; elevated Sun2 promotes RhoA activation and F-actin polymerization leading to nuclear stiffening. siRNA knockdown of Sun2 in WT and HGPS-model MSCs, cyclic mechanical stretch, nuclear deformability assays, RhoA/F-actin quantification, γH2AX measurement Cell death discovery Medium 37198162
2024 SUN2 promotes flavivirus (ZIKV, DENV, JEV) replication by facilitating cytoskeleton rearrangement and replication organelle formation; SUN2 is required for interaction between actin and ZIKV NS1, and dominant-negative Nesprin-1/2 (which link SUN2 to the cytoskeleton) reduces this actin–NS1 interaction and viral replication. CRISPR/Cas9 SUN2 knockout, dominant-negative Nesprin expression, co-immunoprecipitation (actin–NS1 interaction), viral RNA synthesis assay, neonatal mouse ZIKV infection model Nature communications High 38177122
2024 Calcium elevations trigger rapid nuclear actin assembly requiring SUN2 independently of its LINC complex function; SUN2 co-localizes and associates with the formin INF2 at the nuclear envelope in a calcium-regulated manner, and SUN2 is required for active RNA Pol II clustering in response to calcium elevations. siRNA knockdown, live-cell imaging of nuclear actin, co-immunoprecipitation of SUN2 with INF2, RNA Pol II clustering assay, calcium manipulation EMBO reports High 39317734
2026 Paclitaxel induces nuclear aberrations in interphase through SUN2-dependent disruption of lamin A/C; paclitaxel treatment causes aberrant microtubule-vimentin bundle formation, and SUN2 mediates lamin A/C reduction through polyubiquitylation. Lamin A/C levels in turn determine cell survival and recovery after drug treatment. Advanced optical imaging, electron cryo-tomography, SUN2 knockdown/knockout, ubiquitylation assays, lamin A/C quantification, cell survival assays Journal of cell science High 41367359
2026 Sun2 is required for stiffness-dependent upregulation of extracellular matrix genes during lung fibrosis; Sun2-null fibroblasts can still become contractile myofibroblasts in response to TGFβ but fail to upregulate ECM protein-encoding genes, preventing fibrosis development in bleomycin-treated mice. Sun2-null mice, bleomycin lung fibrosis model, primary fibroblast substrate stiffness assays, gene expression analysis bioRxivpreprint Medium 41889916
2026 SUN2 mediates stiffness-dependent chromatin regulation during skin fibrosis: on stiff substrates, SUN2 is required for changes in nuclear size, three distinct mechanosensitive chromatin states, and mechanical induction of the histone methyltransferase EZH2; loss of Sun2 abolishes stiffness-induced fibrotic gene expression and protects against bleomycin-induced skin fibrosis. Sun2 knockout, bleomycin skin fibrosis model, substrate stiffness experiments, chromatin state analysis, EZH2 assays in dermal fibroblasts bioRxivpreprint Medium 41890082
2026 Farnesylated prelamin A inhibits nesprin-2/SUN2 LINC complex function by reducing the diffusional mobility of nesprin-2 and SUN2, thereby impairing actin-force transmission to the nucleus and causing cell polarity defects; this effect depends on the farnesyl moiety in the prelamin A tail. FRAP for diffusional mobility, nuclear repositioning/polarity assays, expression of tail fragments and farnesylation mutants in fibroblasts Journal of cell science High 42011117

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proceedings of the National Academy of Sciences of the United States of America 197 19509342
2004 Sun2 is a novel mammalian inner nuclear membrane protein. The Journal of biological chemistry 169 15082709
2014 Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization. PLoS genetics 138 25210889
2007 Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proceedings of the National Academy of Sciences of the United States of America 134 17452644
2015 Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer. Cancer medicine 121 26175118
2012 Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Current biology : CB 90 22863315
2015 Absence of SUN1 and SUN2 proteins in Arabidopsis thaliana leads to a delay in meiotic progression and defects in synapsis and recombination. The Plant journal : for cell and molecular biology 85 25412930
2015 SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer. Scientific reports 78 26658802
2010 A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane. The EMBO journal 78 20551905
2018 Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis. Cell death & disease 53 30282980
2022 FBXO2 targets glycosylated SUN2 for ubiquitination and degradation to promote ovarian cancer development. Cell death & disease 44 35525855
2016 Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication. Cell reports 42 27149839
2016 SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV. Journal of virology 41 26865710
2022 Regulated degradation of the inner nuclear membrane protein SUN2 maintains nuclear envelope architecture and function. eLife 34 36318477
2021 Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention. Journal of experimental & clinical cancer research : CR 34 33648524
2011 Subcellular localization of SUN2 is regulated by lamin A and Rab5. PloS one 28 21655223
2014 Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors. Carcinogenesis 27 24832085
2018 SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin. mBio 26 29717016
2012 Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment. Histochemistry and cell biology 26 22706480
2019 Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis. Molecular biology of the cell 24 31091167
2017 SUN2 Silencing Impairs CD4 T Cell Proliferation and Alters Sensitivity to HIV-1 Infection Independently of Cyclophilin A. Journal of virology 22 28077629
2023 Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence. Cell death discovery 20 37198162
2021 Downregulation of SUN2 promotes metastasis of colon cancer by activating BDNF/TrkB signalling by interacting with SIRT1. The Journal of pathology 19 33931868
2018 A molecular model for LINC complex regulation: activation of SUN2 for KASH binding. Molecular biology of the cell 18 29995584
2017 Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the Early Steps of HIV-1 Infection. Journal of virology 18 28747499
2022 SUN2 regulates mitotic duration in response to extracellular matrix rigidity. Proceedings of the National Academy of Sciences of the United States of America 17 36322767
2018 SUN2: A potential therapeutic target in cancer. Oncology letters 17 30675193
2017 Loss of Sun2 promotes the progression of prostate cancer by regulating fatty acid oxidation. Oncotarget 17 29163775
2024 Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1. Nature communications 16 38177122
2023 Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2. Cell reports 16 37210724
2023 Disulfide bond in SUN2 regulates dynamic remodeling of LINC complexes at the nuclear envelope. Life science alliance 12 37188462
2024 SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II. EMBO reports 11 39317734
2020 Elevated Sad1 and UNC84 Domain Containing 2 (SUN2) level inhibits cell growth and aerobic glycolysis in oral cancer through reducing the expressions of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). Journal of dental sciences 6 33384835
2023 Physcomitrium patens SUN2 Mediates MTOC Association with the Nuclear Envelope and Facilitates Chromosome Alignment during Spindle Assembly. Plant & cell physiology 5 37421143
2022 SUN2 Modulates the Propagation of HSV-1. Journal of virology 5 35435724
2024 Long non-coding RNA SUN2-AS1 acts as a negative regulator of ISGs transcription to promote flavivirus infection. Virology 1 39288611
2026 Paclitaxel compromises nuclear integrity in interphase through SUN2-mediated cytoskeletal coupling. Journal of cell science 0 41367359
2026 Loss of Sun2 ablates nuclear mechanosensing-driven extracellular matrix production and mitigates lung fibrosis. bioRxiv : the preprint server for biology 0 41889916
2026 SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis. bioRxiv : the preprint server for biology 0 41890082
2026 Farnesylated prelamin A induces fibroblast polarity defects in premature aging disorders by inhibiting nesprin-2-SUN2 LINC complex function. Journal of cell science 0 42011117
2025 SUN2 downregulation promotes breast cancer cell proliferation via NFATC4 upregulation. Biochemical and biophysical research communications 0 41308440