Affinage

SUN2

SUN domain-containing protein 2 · UniProt Q9UH99

Length
717 aa
Mass
80.3 kDa
Annotated
2026-06-10
41 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUN2 is an integral inner nuclear membrane (INM) protein that forms the nucleoplasmic half of the LINC complex, physically coupling the nucleoskeleton to the cytoskeleton and serving as a node for mechanotransduction, nuclear positioning, and genome organization (PMID:15082709, PMID:19509342). It localizes to the INM through three redundant signals—an N-terminal classical NLS, an adjacent coatomer-dependent Golgi-retrieval arginine cluster, and the C-terminal lumenal SUN domain—and its NE retention further depends on correctly processed lamin A (PMID:20551905, PMID:21655223). Functional LINC assembly requires SUN2 to convert from an autoinhibited monomer to a CC1/CC2 coiled-coil-stabilized trimer competent to bind KASH-domain nesprins, a transition reinforced by KASH-dependent disulfide-bond rearrangements among conserved SUN-domain cysteines whose redox state is set by the ER lumen (PMID:29995584, PMID:37188462). Through these nesprin connections SUN2 retains Syne-1/Nesprin-1 at the muscle NE to position myonuclei and tethers meiotic telomeres to the envelope for their dynamic movement (PMID:17452644, PMID:19509342). SUN2 transmits mechanical force from ECM stiffness across the NE, driving mitotic spindle and astral-microtubule organization, stiffness-dependent fibrotic gene programs via EZH2-mediated chromatin remodeling, and direct LINC tension measurable in living cells [PMID:36322767, PMID:bio_10.1101_2025.02.17.638756, PMID:41890082]. SUN2 also gates genome function and stress responses—supporting DNA-damage signaling via the DNA-PK complex, associating with the actin nucleator INF2 to drive calcium-triggered nuclear actin assembly and RNA Pol II clustering, and participating in pre-mRNA splicing of sororin (PMID:22863315, PMID:39317734, PMID:33648524). SUN2 abundance is tightly controlled by CK2 phosphorylation that licenses SCFβTrCP ubiquitination and p97-dependent proteasomal extraction, opposed by the phosphatase CTDNEP1, and by FBXO2-mediated recognition of glycosylated SUN2 (PMID:36318477, PMID:35525855). In viral infection SUN2 both restricts and supports HIV-1 at the nuclear envelope through capsid/CypA- and lamin A/C–chromatin-dependent mechanisms and is required for flavivirus replication by bridging actin to viral NS1 (PMID:26865710, PMID:29717016, PMID:38177122).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2004 High

    Established that SUN2 is an INM protein with its SUN domain in the perinuclear lumen, defining the topology required for any nucleoskeleton-cytoskeleton bridging function.

    Evidence Tagged deletion constructs, fractionation, EM, and marker co-localization in mammalian cells

    PMID:15082709

    Open questions at the time
    • Binding partners on either membrane face not yet identified
    • No functional readout of LINC bridging
  2. 2007 High

    Showed SUN2 marks NE attachment sites of meiotic telomeres within a membrane-spanning fibrillar complex, the first concrete role linking SUN2 to coupling nuclear contents to cytoplasmic structures.

    Evidence Immunofluorescence, EM, and lamin A-null / axial element-null mouse genetics

    PMID:17452644

    Open questions at the time
    • Cytoplasmic partner mediating telomere movement not defined
    • Whether SUN2 is essential versus redundant for bouquet formation unresolved
  3. 2009 High

    Demonstrated SUN1/SUN2 functional redundancy in retaining nesprin at the NE and positioning myonuclei, establishing the genetic logic of LINC dosage in tissue.

    Evidence Sun1/Sun2 single and double knockout mice with nesprin localization and myonuclear positioning readouts

    PMID:19509342

    Open questions at the time
    • Direct SUN2–Syne-1 interaction interface not mapped here
    • Tissue specificity of redundancy unclear
  4. 2010 High

    Answered how SUN2 reaches the INM, revealing reliance on a cNLS, a coatomer-retrieval signal, and the SUN domain together.

    Evidence Systematic mutagenesis, live imaging, coatomer-binding and Golgi-disruption assays

    PMID:20551905

    Open questions at the time
    • Relative weight of each signal in physiological context not quantified
  5. 2011 Medium

    Linked SUN2 NE retention to lamin A and implicated SUN2 in endocytic transferrin uptake via Rab5, broadening its localization dependencies and possible roles.

    Evidence Lamin A/C rescue, Rab5 perturbation, and transferrin uptake assays

    PMID:21655223

    Open questions at the time
    • Mechanism of SUN2–Rab5 endocytic role shallow
    • Single lab; physiological relevance of endosomal pool unclear
  6. 2012 Medium

    Placed SUN1/SUN2 upstream of DNA-damage signaling through physical association with the DNA-PK complex and DDR phenotypes in DKO cells.

    Evidence Sun1/Sun2 DKO MEFs, Co-IP screen, γH2AX/pATM imaging, DNAPK knockdown

    PMID:22863315

    Open questions at the time
    • Interaction from a screen; reciprocal validation limited
    • Functional link to DNAPK correlative
  7. 2016 Medium

    Defined SUN2 as a modulator of HIV-1 at the nuclear envelope, with capsid/CypA-dependent restriction mapping to its lamin-interacting nucleoplasmic domain and an opposing endogenous requirement for productive infection.

    Evidence Overexpression and knockdown in cell lines and primary CD4+ T cells, capsid mutant selection, CypA perturbation

    PMID:26865710 PMID:27149839

    Open questions at the time
    • Dual restrictive/supportive role mechanistically unreconciled
    • Direct capsid contact not shown in these studies
  8. 2017 Medium

    Showed direct physical capture of SUN2 by HIV-1 capsid and that SUN2 also supports CD4+ T-cell proliferation and viability, complicating its net effect on infection.

    Evidence CRISPR knockout, CANC nanotube pulldown, proliferation/activation assays

    PMID:28077629 PMID:28747499

    Open questions at the time
    • Phenotypes modest
    • Whether T-cell fitness effect confounds infection readouts
  9. 2018 Medium

    Revealed a chromatin-level role: SUN2 with lamin A/C tethers and silences the HIV-1 5'-LTR, blocking RNA Pol II recruitment and enforcing latency.

    Evidence Co-IP, ChIP, knockdown/overexpression, latency reactivation assays

    PMID:29717016

    Open questions at the time
    • Generalization beyond LTR to host genes untested
    • Single lab
  10. 2018 Medium

    Provided the structural logic of LINC assembly, showing trimerization driven by CC1/CC2 interplay relieves SUN-domain autoinhibition to enable KASH binding.

    Evidence Molecular dynamics simulation, gel filtration, E452 mutagenesis

    PMID:29995584

    Open questions at the time
    • No crystal structure of full-length trimer
    • Proposed Ca2+ regulation not directly demonstrated
  11. 2021 Medium

    Uncovered an unexpected spliceosome-associated function, with SUN2 required for sororin pre-mRNA splicing and sister chromatid cohesion in cancer cells.

    Evidence Pulldown-MS, RNAi, intron-retention RT-PCR, FACS in TNBC cells

    PMID:33648524

    Open questions at the time
    • How an INM protein engages the spliceosome unexplained
    • Single lab; cancer-specific context
  12. 2022 High

    Defined the proteostatic control of SUN2: a CK2–SCFβTrCP–p97 degradation axis opposed by CTDNEP1, with a parallel FBXO2/SOX6 route for glycosylated SUN2.

    Evidence In vitro kinase/ubiquitination reconstitution, degron mutants, p97 inhibition, CTDNEP1 knockdown; separate FBXO2 Co-IP and ubiquitination assays

    PMID:35525855 PMID:36318477

    Open questions at the time
    • Trigger for CK2 phosphorylation in vivo unclear
    • Crosstalk between the two degradation routes unknown
  13. 2022 Medium

    Connected SUN2 to mechanically driven mitosis, with ECM stiffness raising SUN2 to organize astral microtubules and license anaphase onset.

    Evidence Defined-stiffness gels, SUN2 knockdown/overexpression, live mitosis imaging

    PMID:36322767

    Open questions at the time
    • Molecular link from SUN2 to spindle apparatus not resolved
    • Single lab
  14. 2023 High

    Established redox control of SUN2, with KASH-dependent disulfide rearrangements governing localization, turnover, LINC assembly, and migration.

    Evidence Conformation-specific antibody, cysteine mutants, FRAP, migration assays, ER redox perturbation

    PMID:37188462

    Open questions at the time
    • ER lumenal oxidoreductase responsible not identified
  15. 2023 Medium

    Identified SUN2 as a transducer of nucleoplasmic protein aggregation to the ER, with its clustering required for progerin-triggered ER stress.

    Evidence Knockdown/overexpression, clustering mutants, ER stress reporters in HGPS cells

    PMID:37210724

    Open questions at the time
    • Signal relayed across membrane to ER lumen undefined
    • Single lab
  16. 2024 High

    Showed SUN2-specific support of flavivirus replication by bridging cytoskeletal actin to viral NS1 for replication organelle formation.

    Evidence CRISPR KO, actin–NS1 Co-IP, dominant-negative nesprin, viral RNA assays, neonatal mouse model across three viruses

    PMID:38177122

    Open questions at the time
    • Whether SUN2 directly contacts NS1 versus via actin unresolved
  17. 2024 Medium

    Revealed a LINC-independent role for SUN2 in calcium-triggered nuclear actin assembly via INF2, coupling calcium signaling to RNA Pol II clustering.

    Evidence Calcium stimulation, knockdown/knockout, SUN2–INF2 Co-IP, nuclear actin and Pol II imaging

    PMID:39317734

    Open questions at the time
    • How INM SUN2 nucleates nucleoplasmic actin geometrically unclear
    • Single lab
  18. 2025 Medium

    Directly measured LINC tension across SUN2 in living cells, showing force transmission scales with contractility and stiffness and varies spatially in vivo.

    Evidence FRET tension sensors inserted into SUN2, live-cell and zebrafish notochord imaging (preprint)

    PMID:bio_10.1101_2025.02.17.638756

    Open questions at the time
    • Preprint, not peer-reviewed
    • Sensor insertion effects on native function not fully controlled
  19. 2026 Medium

    Defined SUN2 as a mechanical coincidence detector driving stiffness-dependent fibrotic gene programs through EZH2/H3K27me3 chromatin remodeling, with loss preventing organ fibrosis in vivo.

    Evidence Sun2 knockout mice, bleomycin lung and skin fibrosis models, stiffness gels, EZH2/H3K27me3 ChIP and expression profiling (preprints)

    PMID:41889916 PMID:41890082

    Open questions at the time
    • Preprints, not peer-reviewed
    • Path from LINC tension to EZH2 induction not molecularly traced
  20. 2026 Medium

    Connected SUN2 mobility defects to laminopathy mechanism, with farnesylated prelamin A immobilizing the nesprin-2/SUN2 LINC complex to impair actin-driven nuclear positioning and cell polarization.

    Evidence FRAP of nesprin-2 and SUN2, farnesylation-deficient prelamin A and tail-fragment expression, polarization assays

    PMID:42011117

    Open questions at the time
    • Direct prelamin A–SUN2 contact versus indirect lamina effect not separated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SUN2's diverse roles—LINC bridging, mechanosensing-to-chromatin signaling, splicing, nuclear actin, and viral modulation—are coordinated within a single protein, and how force across the SUN domain is converted into transcriptional and chromatin outputs, remains unresolved.
  • No unified model linking mechanical input to chromatin/transcriptional output
  • Structural basis of force transmission through trimeric SUN2 unsolved
  • Reconciliation of restrictive versus supportive viral roles missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005635 nuclear envelope 3 GO:0000228 nuclear chromosome 2 GO:0005783 endoplasmic reticulum 2 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-73894 DNA Repair 1
Partners
CTDNEP1FBXO2INF2LMNAPRKDCSYNE1SYNE2VCP
Complex memberships
LINC complexspliceosome

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SUN2 is an inner nuclear membrane (INM) protein in mammalian cells; a truncated form spanning amino acids 26–339 is sufficient for nuclear envelope localization, and its C-terminal SUN domain resides in the perinuclear lumenal space between inner and outer nuclear membranes. Recombinant EGFP/V5-tagged constructs, subcellular fractionation, electron microscopy, antibody co-localization with INM and nuclear pore markers The Journal of biological chemistry High 15082709
2007 SUN2 specifically localizes to the nuclear envelope attachment sites of meiotic telomeres throughout their dynamic movement; EM reveals SUN2 is part of a membrane-spanning fibrillar complex interconnecting attached telomeres with cytoplasmic structures. This association does not require axial element assembly or A-type lamins. Immunofluorescence co-localization, electron microscopy, genetic ablation (lamin A-null, axial element-null mice) Proceedings of the National Academy of Sciences of the United States of America High 17452644
2009 SUN1 and SUN2 function redundantly to retain Syne-1/Nesprin-1 at the nuclear envelope in skeletal muscle cells; loss of both SUN1 and SUN2 disrupts Syne-1 NE localization and causes defective myonuclear positioning (both synaptic and nonsynaptic), demonstrating a dosage-dependent genetic interaction. Sun1 and Sun2 single and double knockout mice, immunofluorescence for Syne-1 at NE, assessment of myonuclear positioning Proceedings of the National Academy of Sciences of the United States of America High 19509342
2010 INM targeting of SUN2 requires three redundant elements: (1) a classical NLS (cNLS) in its N-terminal nucleoplasmic domain, (2) an adjacent arginine cluster that mediates coatomer-dependent Golgi retrieval, and (3) the C-terminal lumenal SUN domain, making SUN2 the first mammalian INM protein relying on a cNLS, Golgi retrieval signal, and perinuclear domain for targeting. Deletion/mutation constructs, live-cell fluorescence imaging, coatomer binding assays, pharmacological Golgi disruption The EMBO journal High 20551905
2011 Lamin A (but not lamin C) is required for NE localization of SUN2; overexpression of Rab5 redistributes SUN2 to endosomes via its SUN domain; endogenous SUN2 co-localizes with Rab5 and overexpression of SUN2 stimulates transferrin uptake while SUN2 knockdown attenuates it, indicating a role in endocytosis. Lamin A/C-deficient cells rescued with lamin A or C, Rab5 overexpression/dominant-negative transfection, transferrin uptake assay, co-localization imaging PloS one Medium 21655223
2012 SUN1 and SUN2 interact biochemically with the DNA-PK complex (Ku70/Ku80/DNA-PKcs) at the nuclear envelope; in Sun1/Sun2 double-knockout MEFs, activation of ATM and H2AX phosphorylation following DNA damage is impaired, and cells show premature S-phase arrest, increased apoptosis, and reduced perinuclear heterochromatin, placing SUN1/SUN2 upstream of DDR signaling. Sun1/Sun2 DKO mouse embryonic fibroblasts, biochemical co-immunoprecipitation screen, immunofluorescence for γH2AX/pATM, cell cycle FACS, DNAPK knockdown Current biology : CB Medium 22863315
2012 Accumulation of farnesylated prelamin A (as in mandibuloacral dysplasia type A) alters SUN2 distribution at the NE, causing a disorganized lattice; treatment with statins (farnesyltransferase inhibitors) partially rescues proper SUN2 organization, establishing that SUN2 localization depends on correctly processed lamin A. Patient-derived MADA fibroblasts, statin/FTI drug treatment, immunofluorescence for SUN2 Histochemistry and cell biology Medium 22706480
2016 SUN2 overexpression blocks HIV-1 infection between reverse transcription and nuclear entry in a capsid-specific manner; a single-amino-acid change in HIV capsid confers resistance; both HIV inhibition and nuclear shape deformation by SUN2 overexpression map to the nucleoplasmic/lamin-interacting domain of SUN2; cyclophilin A (CypA) is implicated in the SUN2-imposed block. Overexpression in cell lines and primary MDCs, passaging-selected capsid mutants, domain deletion mapping, chemical/genetic CypA inhibition, fluorescence imaging of nuclear shape Journal of virology Medium 26865710
2016 Endogenous SUN2 at the inner nuclear membrane is required for CypA-dependent positive effects of wild-type HIV on reverse transcription and nuclear import of viral cDNA in primary CD4+ T cells; CypA-resistant capsid mutants are not restricted by SUN2. SUN2 siRNA knockdown in primary CD4+ T cells, CypA inhibitor/knockdown, infection with wild-type and capsid mutant HIV-1/HIV-2/SIVmac Cell reports Medium 27149839
2017 SUN2 silencing in primary CD4+ T cells impairs their proliferative capacity, activation marker expression, and viability, and reduces viral protein expression in infected cells; the reduced HIV infection in SUN2-silenced CD4 T cells is independent of CypA. SUN2 siRNA in primary CD4+ T cells, proliferation assays, flow cytometry for activation markers, HIV infection assays with CypA inhibition Journal of virology Medium 28077629
2017 CRISPR/Cas9-assembled CANC nanotubes captured both SUN1 and SUN2 from cell lysates, indicating physical interaction between HIV-1 capsid and SUN2; SUN2-/- CRISPR cells show a modest suppressive effect on HIV-1 infectivity. CRISPR/Cas9 knockout, in vitro capsid-nucleocapsid nanotube pulldown from cell lysates, HIV infectivity assay Journal of virology Medium 28747499
2018 SUN2 maintains repressive chromatin at the HIV-1 5'-LTR by associating with lamin A/C; lamin A/C tethers SUN2 to nucleosomes 1 and 2 of the HIV-1 5'-LTR, blocking RNA Pol II phosphorylation and recruitment; SUN2 knockdown converts LTR chromatin to an active state and reactivates HIV from latency; TNF-α-induced reactivation disrupts the SUN2–lamin A/C association. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), SUN2 knockdown/overexpression, HIV latency reactivation assays, RNA Pol II phosphorylation analysis mBio Medium 29717016
2018 Full-length SUN2 must trimerize (mediated by coiled-coil regions CC1 and CC2) to bind KASH-domain proteins; CC2-SUN alone forms an autoinhibited monomer; CC1–CC2 interplay releases autoinhibition; residue E452 on CC1 is involved in the monomer–trimer transition; Ca2+-dependent regulation of this transition is proposed. Molecular dynamics simulation (~1 µs), gel filtration analysis, 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 or upregulation of pathological hypertrophy markers; in the absence of SUN2, MAN1 (a negative regulator of TGFβ signaling) accumulates at the NE, suppressing profibrotic TGFβ signaling, uncoupling hypertrophy from fibrosis. Sun2-/- mice, cardiac morphometry, Western blot for AKT/MAPK, MAN1 and TGFβ pathway markers, nuclear fractionation Molecular biology of the cell Medium 31091167
2021 SUN2 is a component of the spliceosome complex (associated with SNRPD2, SNRPD3, NHP2L1-containing complex) and is required for efficient sororin (CDCA5) pre-mRNA splicing; SUN2 depletion increases sororin intron 1 retention, downregulates SMC1/MAU2/ESPL1, and inhibits TNBC cell proliferation via disruption of sister chromatid cohesion. Pulldown followed by mass spectrometry (protein–protein interaction), RNAi screen, RT-PCR for intron retention, FACS, western blot Journal of experimental & clinical cancer research : CR Medium 33648524
2022 Casein Kinase 2 (CK2) phosphorylates SUN2, enabling binding of the SCFβTrCP ubiquitin ligase which ubiquitinates SUN2; ubiquitinated SUN2 is then extracted from the membrane by the AAA ATPase p97 and delivered to the proteasome for degradation; the phosphatase CTDNEP1 opposes CK2 to stabilize SUN2. Accumulation of non-degradable SUN2 causes aberrant nuclear architecture, DNA damage vulnerability, and increased lagging chromosomes. In vitro kinase/ubiquitination assays, co-immunoprecipitation, phosphomimetic/non-degradable mutants, p97 inhibition, CTDNEP1 knockdown, nuclear morphology and mitosis assays eLife High 36318477
2022 FBXO2, an E3 ubiquitin ligase, recognizes glycosylated SUN2 and targets it for ubiquitin-proteasome-dependent degradation; this mechanism is driven upstream by transcription factor SOX6 promoting FBXO2 expression, defining a SOX6–FBXO2–SUN2 axis in ovarian cancer. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, FBXO2 overexpression/knockdown, glycosylation analysis, TCGA/GEO data integration Cell death & disease Medium 35525855
2022 ECM rigidity upregulates SUN2 expression, and SUN2 in turn promotes metaphase-to-anaphase transition by facilitating mitotic spindle/astral microtubule organization; on soft ECM, low SUN2 levels perturb astral microtubule organization and delay anaphase onset. Polyacrylamide gels of defined stiffness, SUN2 knockdown/overexpression, live-cell mitosis imaging, microtubule organization analysis Proceedings of the National Academy of Sciences of the United States of America Medium 36322767
2023 Conserved cysteines in the SUN domain undergo KASH-dependent inter- and intra-molecular disulfide bond rearrangements; disruption of the terminal disulfide bond compromises SUN2 localization, turnover, LINC complex assembly, cytoskeletal organization, and cell migration; ER lumen components regulate SUN2 cysteine redox state. Conformation-specific SUN2 antibody, biochemical disulfide-bond analysis, cysteine mutants, FRAP, cell migration assays, pharmacological/genetic ER redox perturbation Life science alliance High 37188462
2023 Aggregation of progerin at the NE triggers ER stress in a SUN2-dependent manner; the ability of SUN2 to cluster in the nuclear membrane is required for this ER stress induction, identifying SUN2 as a sensor/transducer of nucleoplasmic protein aggregates to the ER lumen. SUN2 knockdown/overexpression, SUN2 clustering mutants, ER stress reporter assays, live imaging in HGPS cells Cell reports Medium 37210724
2024 SUN2 (but not SUN1) is required for Zika, dengue, and Japanese encephalitis virus replication; mechanistically, SUN2 facilitates cytoskeleton rearrangement and replication organelle formation by mediating the interaction between cytoskeletal actin and viral NS1; dominant-negative nesprin-1/2 (which connect SUN2 to cytoskeleton) reduces actin–NS1 interaction and viral replication. CRISPR/Cas9 SUN2 KO, co-immunoprecipitation of actin with NS1, dominant-negative nesprin constructs, viral RNA synthesis assays, neonatal mouse in vivo infection model Nature communications High 38177122
2024 Calcium elevations trigger rapid nuclear actin assembly requiring SUN2 independently of its LINC complex role; SUN2 co-localizes and associates with the formin/actin nucleator INF2 at the nuclear envelope in a calcium-regulated manner; SUN2 is required for active RNA Pol II clustering in response to calcium elevations. Calcium stimulation, SUN2 knockdown/knockout, co-immunoprecipitation of SUN2 with INF2, fluorescence imaging of nuclear actin and RNA Pol II clusters EMBO reports Medium 39317734
2025 Paclitaxel induces nuclear aberrations in interphase through SUN2-dependent disruption of lamin A/C levels and organization; SUN2 is required for lamin A/C reduction upon paclitaxel treatment and is regulated by polyubiquitylation; aberrant microtubule-vimentin bundles form during paclitaxel treatment coincident with SUN2-mediated nuclear deformation. Optical imaging, electron cryo-tomography, SUN2 knockdown/overexpression, lamin A/C quantification, ubiquitination assays Journal of cell science Medium 41367359
2025 FRET-based nuclear tension sensors (NuTS2) placed across SUN2 measure tension forces transmitted through the LINC complex in living cells; NuTS2 reveals that force transmission across SUN2 increases with cell contractility and matrix stiffness, occurs dynamically during adhesion, migration, and nuclear squeeze, and shows a gradient increasing from posterior to anterior in zebrafish notochord cells as vacuoles expand. Genetically encoded FRET tension sensors inserted into SUN2, live-cell imaging, zebrafish notochord in vivo imaging, mechanical perturbations bioRxivpreprint Medium bio_10.1101_2025.02.17.638756
2026 Sun2 is required for stiffness-dependent upregulation of ECM protein genes in lung fibroblasts; loss of Sun2 prevents lung fibrosis in bleomycin-treated mice without impairing myofibroblast formation or TGFβ responsiveness per se, indicating Sun2 acts as a mechanical coincidence detector for ECM gene induction. Sun2 knockout mice, bleomycin lung fibrosis model, substrate stiffness gels, gene expression profiling, TGFβ treatment bioRxivpreprint Medium 41889916
2026 SUN2 mediates stiffness-dependent epigenetic remodeling in dermal fibroblasts; loss of Sun2 prevents bleomycin-induced skin fibrosis and abolishes stiffness-induced nuclear size changes and fibrotic gene expression; mechanistically, Sun2 is required for mechanical induction of the histone methyltransferase EZH2, defining three Sun2-dependent mechanosensitive chromatin states. Sun2 knockout mice, bleomycin skin fibrosis model, substrate stiffness gels, histone ChIP for H3K27me3, EZH2 western blot/knockdown, nuclear morphometry bioRxivpreprint Medium 41890082
2026 Farnesylated prelamin A variants reduce diffusional mobilities of nesprin-2 and SUN2 at the NE and impair their function in actin-driven nuclear rearward movement for cell polarization in a farnesylation-dependent manner; short C-terminal tail fragments of prelamin A variants are sufficient to disrupt polarity, identifying inhibition of the nesprin-2/SUN2 LINC complex as the common mechanism in prelamin A-related premature aging syndromes. FRAP for nesprin-2 and SUN2 mobility, cell polarization assays, expression of farnesylation-deficient prelamin A mutants, tail fragment expression Journal of cell science Medium 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 199 19509342
2004 Sun2 is a novel mammalian inner nuclear membrane protein. The Journal of biological chemistry 170 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 122 26175118
2012 Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Current biology : CB 90 22863315
2010 A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane. The EMBO journal 79 20551905
2015 SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer. Scientific reports 78 26658802
2018 Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis. Cell death & disease 55 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 37 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 35 33648524
2011 Subcellular localization of SUN2 is regulated by lamin A and Rab5. PloS one 29 21655223
2018 SUN2 Modulates HIV-1 Infection and Latency through Association with Lamin A/C To Maintain the Repressive Chromatin. mBio 27 29717016
2014 Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors. Carcinogenesis 27 24832085
2019 Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis. Molecular biology of the cell 26 31091167
2012 Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment. Histochemistry and cell biology 26 22706480
2023 Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence. Cell death discovery 24 37198162
2017 SUN2 Silencing Impairs CD4 T Cell Proliferation and Alters Sensitivity to HIV-1 Infection Independently of Cyclophilin A. Journal of virology 22 28077629
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 19 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 19 28747499
2024 Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1. Nature communications 17 38177122
2023 Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2. Cell reports 17 37210724
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
2023 Disulfide bond in SUN2 regulates dynamic remodeling of LINC complexes at the nuclear envelope. Life science alliance 13 37188462
2024 SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II. EMBO reports 11 39317734
2022 SUN2 Modulates the Propagation of HSV-1. Journal of virology 6 35435724
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
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
2026 Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function. bioRxiv : the preprint server for biology 0 42239109
2025 SUN2 downregulation promotes breast cancer cell proliferation via NFATC4 upregulation. Biochemical and biophysical research communications 0 41308440

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