Affinage

SOHLH2

Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2 · UniProt Q9NX45

Length
425 aa
Mass
46.9 kDa
Annotated
2026-06-10
35 papers in source corpus 26 papers cited in narrative 26 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

SOHLH2 is a germ cell-specific basic helix-loop-helix (bHLH) transcription factor that governs premeiotic germ cell differentiation and, in somatic tissues, acts as a context-dependent transcriptional regulator of proliferation, invasion, and stress responses (PMID:16765102, PMID:18339773). In the male germline, SOHLH2 is required for progression of differentiating type A spermatogonia to type B; its loss arrests differentiation and deranges cell-surface cKit expression (PMID:18339773). It functions in obligate partnership with SOHLH1: the two factors heterodimerize (and SOHLH2 can homodimerize), are mutually co-expressed across the spermatogonial population, and act synergistically, with SOHLH2 nuclear translocation depending on SOHLH1 (PMID:19014927, PMID:22056784, PMID:28504655). Together they bind E-box motifs to directly activate Kit—cooperatively transactivating its promoter and first intron—and to auto-regulate Sohlh1 transcription through a ternary complex with SP1, while repressing the SSC-maintenance and meiotic-entry programs by suppressing Gfra1, Sox3, and Stra8 (PMID:22056784, PMID:22328502, PMID:25003626, PMID:25603532). SOHLH2 acts downstream of BMP4/SMAD signaling and upstream of cKit, and protects oocytes from apoptosis via a cKit/PI3K/Akt/Foxo3a axis (PMID:23212987, PMID:24591295, PMID:25773528). SOHLH2 is also essential for synaptonemal complex formation, directly binding and activating the Sycp1 promoter (PMID:26869299). In cancer and somatic disease contexts, SOHLH2 binds target promoters to repress oncogenic and pro-invasive genes—MMP9, IL-8, HIF1α, cyclin D1, LXRα, H19—and to activate tumor-suppressive genes including p21 and APC, with epistasis confirming these targets mediate its anti-proliferative, anti-invasive, and anti-angiogenic effects (PMID:24858206, PMID:26153894, PMID:27384482, PMID:30720232, PMID:34158392, PMID:36287177). SOHLH2 protein abundance is set by ubiquitin-mediated degradation, with TRIM21 and PRMT5-directed CUL4B promoting its turnover (PMID:38123542, PMID:41867089).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2006 Medium

    Established SOHLH2's identity and expression niche, defining it as a germ cell-restricted bHLH factor confined to premeiotic spermatogonia and oocytes.

    Evidence Expression analysis and IHC across mouse gonad development

    PMID:16765102

    Open questions at the time
    • No functional assay or target genes in this study
    • DNA-binding activity not demonstrated
  2. 2008 High

    Defined the in vivo requirement for SOHLH2 in spermatogonial differentiation, showing knockout males arrest at type A2 spermatogonia with aberrant cKit, linking the factor to the cKit differentiation program.

    Evidence Sohlh2 knockout mouse with histology, marker immunostaining, and cultured spermatogonia cKit analysis

    PMID:18339773

    Open questions at the time
    • Direct transcriptional targets not yet identified
    • Mechanism of cKit deregulation unresolved at this stage
  3. 2008 Medium

    Identified SOHLH1 as a SOHLH2 partner and showed SOHLH2 controls Sohlh1 levels, introducing the heterodimer model for KIT+ germ cell differentiation.

    Evidence Co-IP for heterodimerization, knockout, and Sohlh1 expression analysis

    PMID:19014927

    Open questions at the time
    • Direct promoter binding not shown
    • Whether dimerization is required for DNA binding unresolved
  4. 2011 High

    Resolved the dimerization architecture and the dual regulatory logic, demonstrating in vivo hetero- and homodimerization and direct, synergistic regulation of Gfra1, Sox3, and Kit to suppress SSC maintenance and induce differentiation.

    Evidence In vivo reciprocal co-IP, double-knockout genetic epistasis, immunostaining, and gene expression analysis

    PMID:22056784

    Open questions at the time
    • E-box occupancy at Gfra1/Sox3 not directly mapped here
    • Repression versus activation mechanism not biochemically distinguished
  5. 2011 Medium

    Showed SOHLH2 transcription is itself epigenetically gated, with dynamic promoter CpG methylation tracking its expression during gametogenesis.

    Evidence Bisulfite sequencing of promoter/exon/intron loci correlated with transcript levels

    PMID:21427160

    Open questions at the time
    • Causal link between methylation and expression not tested by functional rescue
    • Enzymes establishing the methylation not identified
  6. 2012 High

    Provided direct biochemical proof that SOHLH1/SOHLH2 bind Kit promoter and intronic E-boxes and cooperatively transactivate Kit, establishing Kit as a bona fide direct target.

    Evidence Reporter assays, EMSA, ChIP in spermatogonia, co-IP, and ES cell overexpression

    PMID:22328502

    Open questions at the time
    • Independent versus cooperative contributions of each factor not fully separated
    • Co-activator requirements not defined
  7. 2012 Medium

    Placed SOHLH2 within an upstream BMP4/SMAD signaling input controlling the primordial-to-primary follicle transition.

    Evidence Ovarian organ culture with BMP4, IHC, RT-PCR, and pSMAD Western blotting

    PMID:23212987

    Open questions at the time
    • No knockout or rescue in this system
    • Direct SMAD action on the Sohlh2 promoter not demonstrated
  8. 2014 High

    Uncovered an auto-regulatory loop in which SOHLH2/SOHLH1 and SP1 form a ternary complex to activate Sohlh1 transcription, explaining mutual dependence of the two factors.

    Evidence Reporter/transactivation assays, SOHLH1-SP1 co-IP, and in vivo ChIP in postnatal testes

    PMID:25003626

    Open questions at the time
    • Whether SOHLH2 contacts SP1 directly not resolved
    • Stoichiometry of the ternary complex unknown
  9. 2014 Medium

    Confirmed the BMP4/Smad → Sohlh2 → cKit epistatic order in SSC differentiation through pathway inhibition and RNAi.

    Evidence BMP4 treatment, dorsomorphin inhibition, and Sohlh2 siRNA in cultured SSCs

    PMID:24591295

    Open questions at the time
    • Direct transcriptional connection to cKit in SSCs not re-mapped here
    • In vivo relevance of the inhibitor effect untested
  10. 2014 Medium

    Opened the somatic/oncogenic chapter, defining SOHLH2 as an ovarian cancer tumor suppressor acting through direct p21 upregulation and cyclin D1 downregulation.

    Evidence Gain/loss of function, proliferation assays, xenografts, and p21/cyclin D1 siRNA epistasis

    PMID:24858206

    Open questions at the time
    • Direct promoter occupancy at p21/cyclin D1 not shown here
    • Mechanism switching SOHLH2 between activation and repression unknown
  11. 2015 Medium

    Extended the germline regulatory network by showing SOHLH factors cooperatively repress Stra8 via E-boxes, linking them to control of meiotic entry timing.

    Evidence Reporter assays with E-box mutagenesis and expression analysis in KIT+ spermatogonia

    PMID:25603532

    Open questions at the time
    • In vivo ChIP at the Stra8 promoter not reported
    • Repressive co-factors not identified
  12. 2015 Medium

    Defined the survival pathway by which SOHLH2 protects oocytes, the cKit/PI3K/Akt/Foxo3a anti-apoptotic axis.

    Evidence siRNA/overexpression in oocyte cultures, P-Akt/Foxo3a Western blots, LY294002 rescue, and TUNEL

    PMID:25773528

    Open questions at the time
    • Direct transcriptional step linking SOHLH2 to this axis assumed via cKit
    • In vivo ovarian relevance not tested in this study
  13. 2015 Medium

    Showed SOHLH2 suppresses cancer invasion through direct repression of MMP9, the first promoter-level anti-invasive target.

    Evidence Reporter/binding assays, MMP9 siRNA and ectopic MMP9 epistasis, invasion assays, and metastasis model

    PMID:26153894

    Open questions at the time
    • Co-repressor machinery undefined
    • Single-cancer-type validation
  14. 2016 Medium

    Identified an independent meiotic role for SOHLH2 in synaptonemal complex formation through direct activation of Sycp1.

    Evidence Knockout phenotyping, SYCP3 immunostaining/Western, and Sycp1 promoter reporter with E-box analysis

    PMID:26869299

    Open questions at the time
    • Whether SOHLH1 partnership is required here not resolved
    • Direct regulation of other SC components not tested
  15. 2016 Medium

    Expanded anti-invasive function to breast cancer EMT via direct repression of IL-8.

    Evidence ChIP, luciferase reporter, RNA-seq, IL-8 siRNA/recombinant IL-8 rescue, and metastasis model

    PMID:27384482

    Open questions at the time
    • Cross-talk among repressed invasion targets not integrated
    • Determinants of target selectivity unknown
  16. 2017 High

    Established SOHLH1-dependent nuclear translocation of SOHLH2 and defined its earliest embryonic germline activity, refining the temporal hierarchy of the two factors.

    Evidence Confocal localization in embryonic gonads, Sohlh1 KO localization analysis, and KO expression of LHX8/NOBOX

    PMID:28504655

    Open questions at the time
    • Molecular basis of SOHLH1-dependent nuclear import unknown
    • Whether cytoplasmic SOHLH2 has non-genomic roles untested
  17. 2019 Medium

    Showed SOHLH2 restrains Wnt/β-catenin signaling by directly activating APC, adding a tumor-suppressive activation target.

    Evidence Forced expression/knockdown, proliferation/cell-cycle assays, xenograft, and APC siRNA epistasis

    PMID:30720232

    Open questions at the time
    • Direct APC promoter occupancy not shown
    • Reconciliation with H19/β-catenin pathway in colon cancer not addressed
  18. 2020 Low

    Linked SOHLH2 to hypoxic invasion control via the HIF1α/CA9 axis in ovarian cancer.

    Evidence Overexpression/knockdown under hypoxia with migration/invasion assays and HIF1α/CA9 Western blot

    PMID:31318683

    Open questions at the time
    • No direct promoter binding or rescue in this study
    • Pathway placement rests on expression changes only
  19. 2021 Medium

    Provided direct evidence that SOHLH2 represses angiogenesis by binding and repressing the HIF1α promoter.

    Evidence ChIP, luciferase reporter, HUVEC co-culture, xenograft MVD, and HIF1α rescue

    PMID:34158392

    Open questions at the time
    • Relationship to HIF1α/CA9 invasion findings not unified
    • Hypoxia-dependence of SOHLH2 binding untested
  20. 2022 Low

    Proposed an epigenetic tumor-suppressive route in renal cancer via DNMT3a downregulation and Klotho demethylation.

    Evidence Overexpression/knockdown in RCC lines, DNMT3a/Klotho qPCR-Western, proliferation, xenograft, and patient IHC

    PMID:35127476

    Open questions at the time
    • No direct methylation assay or ChIP for DNMT3a regulation
    • Mechanism inferred from expression correlation
  21. 2023 Medium

    Connected SOHLH2 to tumor immune microenvironment, showing it drives macrophage M2 polarization via direct LXRα activation, and identified TRIM21 as an E3 ligase controlling SOHLH2 turnover.

    Evidence Macrophage overexpression, ChIP/reporter for LXRα, TRIM21 co-IP and ubiquitination assays, and lung metastasis model

    PMID:38123542

    Open questions at the time
    • Degron and ubiquitination sites on SOHLH2 not mapped
    • Reconciliation with tumor-suppressive roles context-dependent and unexplained
  22. 2023 Medium

    Demonstrated SOHLH2 modulates oxidative stress in pulmonary fibrosis by directly repressing p62 and dampening Keap1/Nrf2 signaling.

    Evidence Type II AEC conditional knock-in mouse, A549 overexpression, ROS/apoptosis assays, NAC rescue, and p62 promoter analysis

    PMID:37875506

    Open questions at the time
    • Direct ChIP at the p62 promoter not detailed
    • Relevance beyond AEC unknown
  23. 2023 Medium

    Showed SOHLH2 suppresses cancer stem cell stemness by directly repressing the LncRNA-H19 promoter, feeding the H19/miR-141/β-catenin axis.

    Evidence ChIP, luciferase reporter, H19 rescue/knockdown epistasis, and in vitro/in vivo CSC assays

    PMID:36287177

    Open questions at the time
    • Integration with APC-mediated Wnt control not addressed
    • Determinants of repression vs activation at different promoters unknown
  24. 2024 Medium

    Documented a pro-tumorigenic activity in hepatocellular carcinoma, with SOHLH2 directly activating TGM2 to promote autophagy and progression, underscoring context dependence.

    Evidence Overexpression/knockdown, ChIP/reporter for TGM2, and in vitro/in vivo tumor assays

    PMID:39436118

    Open questions at the time
    • Basis for tumor-promoting versus tumor-suppressing switch unresolved
    • Upstream control of SOHLH2 in HCC undefined
  25. 2026 Medium

    Defined post-translational control of SOHLH2 by PRMT5-directed arginine methylation and CUL4B-mediated degradation, coupled to a Sirt1-activating, NF-κB-repressing endothelial program.

    Evidence Endothelial knock-in mouse, PRMT5/CUL4B co-IP, ubiquitination assay, Sirt1 ChIP/reporter, and lung metastasis model

    PMID:41867089

    Open questions at the time
    • Methylated arginine residues not mapped
    • Interplay between TRIM21 and CUL4B degradation routes unresolved
  26. 2026 Medium

    Linked SOHLH2 to DNA double-strand break repair, showing it activates RAD54L to promote homologous recombination and radioresistance in lung cancer.

    Evidence Overexpression/knockdown, ChIP/reporter for RAD54L, HR repair assay, RAD54L rescue, and radioresistance models

    PMID:41535248

    Open questions at the time
    • Whether HR role extends to germ cell meiotic recombination untested
    • Relationship to SOHLH2 degradation control unexamined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular determinant that switches SOHLH2 between direct transcriptional activation and repression, and between tumor-suppressive and tumor-promoting outputs across tissues, remains unresolved.
  • No structural model of SOHLH2 DNA binding or cofactor selection
  • Co-activator/co-repressor partners that dictate target outcome unidentified
  • Integration of TRIM21 and PRMT5/CUL4B degradation pathways into a unified stability model lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 4 R-HSA-1474165 Reproduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-73894 DNA Repair 1
Partners
CUL4BPRMT5SOHLH1SP1TRIM21
Complex memberships
SOHLH1-SOHLH2 heterodimerSOHLH2/SOHLH1/SP1 ternary complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 SOHLH2 is a germ cell-specific basic helix-loop-helix (bHLH) transcription factor expressed in spermatogonia and oocytes of primordial and primary follicles, confined to premeiotic germ cells. Expression analysis, protein localization by immunohistochemistry in mouse gonads Gene expression patterns : GEP Medium 16765102
2008 SOHLH2 is required for progression of differentiating type A spermatogonia into type B spermatogonia; Sohlh2-null males are infertile due to a block at differentiating type A2 spermatogonia (accumulating in M-phase prior to death), and undifferentiated spermatogonia isolated from null mice show aberrant cell-surface expression of cKit. Sohlh2 knockout mouse generation, histological analysis, immunostaining (DAZL, PLZF), cKit surface expression analysis in cultured spermatogonia Stem cells (Dayton, Ohio) High 18339773
2008 SOHLH2 and SOHLH1 can form heterodimers; Sohlh2 null mice show downregulation of Sohlh1, and both proteins are required for differentiation of KIT+ spermatogonia and oocytes. Co-immunoprecipitation for heterodimerization; gene targeting/knockout; expression analysis of Sohlh1 in null gonads Developmental biology Medium 19014927
2011 SOHLH1 and SOHLH2 heterodimerize with each other in vivo and also homodimerize; they are co-expressed throughout the spermatogonial population except GFRA1+ SSCs; double mutants show synergistic effects on gene expression and increased GFRA1+ population with premature meiosis; SOHLH proteins directly regulate Gfra1, Sox3, and Kit gene expression, suppressing SSC maintenance genes and inducing differentiation genes. In vivo co-immunoprecipitation; double knockout mouse; immunostaining; gene expression analysis Developmental biology High 22056784
2011 DNA CpG methylation in the Sohlh2 promoter region (sohlh2-P: -202 to +173 bp) dynamically changes during germ cell differentiation and correlates with Sohlh2 transcript expression, whereas methylation in first exon/intron regions remains constant. Bisulfite sequencing of promoter, exon, and intron CpG sites during gametogenesis in mouse Molecular human reproduction Medium 21427160
2012 SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia by binding E-box sequences in the Kit promoter and first intron; they can independently and cooperatively bind E-box probes (EMSA); co-expression of both factors cooperatively transactivates Kit promoter and increases endogenous Kit expression in ES cells; SOHLH1 occupies the Kit promoter E-box in spermatogonia chromatin (ChIP). Transfection/promoter reporter assay, EMSA, co-immunoprecipitation, ChIP in spermatogonia, overexpression in ES cells Journal of cell science High 22328502
2012 BMP4/SMAD1/5/8 signaling upregulates Sohlh2 and c-kit expression in primordial follicle oocytes, promoting primordial-to-primary follicle transition and reducing oocyte apoptosis. Ovarian organ culture with BMP4, immunohistochemistry, RT-PCR, Western blotting for pSMAD1/5/8, Sohlh2, c-kit Molecular reproduction and development Medium 23212987
2014 The SOHLH2/SOHLH1/SP1 ternary complex auto-regulates Sohlh1 gene transcription: SOHLH2 and SOHLH1 synergistically upregulate Sohlh1 through E-boxes upstream of its promoter; SOHLH1 binds SP1; both SOHLH1 and SP1 occupy the Sohlh1 promoter in vivo in postnatal testes. Promoter reporter/transactivation assays, co-immunoprecipitation (SOHLH1-SP1 interaction), ChIP in postnatal day 8 mouse testes PloS one High 25003626
2014 BMP4/Smad signaling induces SSC differentiation via upregulation of Sohlh2, which in turn upregulates c-kit; knockdown of Sohlh2 by RNAi abolishes BMP4-induced differentiation and c-kit upregulation, placing Sohlh2 downstream of BMP4/Smad and upstream of c-kit in SSC differentiation. BMP4 treatment of cultured SSCs, Dorsomorphin inhibitor, siRNA knockdown of Sohlh2, Western blot and flow cytometry for differentiation markers Anatomical record (Hoboken, N.J. : 2007) Medium 24591295
2014 Sohlh2 functions as a tumor suppressor in epithelial ovarian cancer by directly upregulating p21 and downregulating cyclin D1 transcription; p21 knockdown reverses the anti-proliferative effect of Sohlh2 overexpression, and cyclin D1 knockdown reverses the pro-proliferative effect of Sohlh2 ablation. Forced expression/knockdown of Sohlh2, MTT/BrdU/colony assays, tumor xenograft, p21 and cyclin D1 siRNA epistasis experiments Carcinogenesis Medium 24858206
2015 SOHLH1 and SOHLH2 directly and cooperatively repress STRA8 expression through two canonical E-box motifs in the Stra8 promoter, establishing a negative transcriptional regulatory link between SOHLH factors and STRA8 in premeiotic germ cells. Promoter reporter assays in cell lines, E-box mutational analysis, expression analysis in KIT+ spermatogonia Cell cycle (Georgetown, Tex.) Medium 25603532
2015 Sohlh2 inhibits apoptosis of primordial follicle oocytes via the c-kit/PI3K/Akt/Foxo3a signaling pathway: Sohlh2 upregulates c-kit, increases phospho-Akt1 and phospho-Foxo3a (reducing nuclear Foxo3a), and the PI3K inhibitor LY294002 blocks Sohlh2's effect on Akt/Foxo3a phosphorylation. Sohlh2 siRNA and overexpression in primary oocyte cultures, Western blot for P-Akt1/Foxo3a, PI3K inhibitor LY294002 rescue, TUNEL apoptosis assay Reproductive biomedicine online Medium 25773528
2015 Sohlh2 inhibits ovarian cancer cell invasion and metastasis by directly binding the MMP9 gene promoter and repressing its transcriptional activity; MMP9 knockdown blocks Sohlh2-ablation-enhanced invasion, and ectopic MMP9 expression compensates for Sohlh2's anti-invasive activity. Promoter reporter assay, ChIP/binding analysis, siRNA knockdown of MMP9, forced expression and silencing of Sohlh2, invasion assay, nude mouse metastasis model Molecular carcinogenesis Medium 26153894
2016 SOHLH2 is essential for synaptonemal complex formation during spermatogenesis; Sohlh2-deficient spermatocytes lack synaptonemal complexes and have reduced SYCP3; SOHLH2 directly binds two E-boxes on the Sycp1 promoter and increases Sycp1 promoter activity. Sohlh2 knockout mouse, gene expression profiling, Western blot and immunostaining for SYCP3, promoter reporter assay with E-box binding analysis Scientific reports Medium 26869299
2016 Sohlh2 suppresses epithelial-to-mesenchymal transition (EMT) and breast cancer cell migration/invasion by binding the IL-8 promoter and repressing its transcription; IL-8 knockdown blocks Sohlh2-ablation-enhanced invasion, and exogenous IL-8 neutralizes Sohlh2's anti-invasive activity. ChIP and luciferase reporter assays for IL-8 promoter, RNA-seq after Sohlh2 knockdown, IL-8 siRNA and recombinant IL-8 rescue experiments, in vivo metastasis model Oncotarget Medium 27384482
2017 SOHLH2 protein is expressed in mouse germline as early as E12.5, preceding SOHLH1 (E15.5); SOHLH2 initially localizes to the cytoplasm and translocates to the nucleus at E15.5 coinciding with SOHLH1 expression; nuclear translocation of SOHLH2 is dependent on SOHLH1. Single deficiency of Sohlh1 or Sohlh2 disrupts LHX8 and NOBOX expression in the embryonic gonad without affecting meiosis. Immunofluorescence/confocal microscopy for SOHLH2 subcellular localization in embryonic gonads; Sohlh1 knockout analysis of SOHLH2 localization; embryonic gonad Sohlh1/Sohlh2 KO expression analysis The Journal of clinical investigation High 28504655
2019 Sohlh2 inhibits breast cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway via direct upregulation of APC transcription; APC knockdown reverses the anti-proliferative effects of Sohlh2 overexpression. Sohlh2 forced expression/knockdown, MTT/BrdU/colony/cell cycle assays, tumor xenograft, APC siRNA epistasis, Western blot for β-catenin pathway components Molecular carcinogenesis Medium 30720232
2020 Sohlh2 inhibits migration, invasion, and EMT of EOC cells under hypoxia through suppression of the HIF1α/CA9 signaling pathway. Sohlh2 overexpression/knockdown in EOC cell lines under hypoxia, migration/invasion assays, Western blot for HIF1α and CA9 Biological chemistry Low 31318683
2021 SOHLH2 suppresses breast cancer angiogenesis by directly binding the HIF1α promoter and repressing its transcriptional activity, thereby downregulating HIF1α-mediated proangiogenic genes; HIF1α upregulation reverses SOHLH2-induced suppression of angiogenesis. ChIP and luciferase reporter assays for HIF1α promoter, SOHLH2 overexpression/knockdown in cancer cells and HUVEC co-culture, in vivo xenograft MVD analysis, HIF1α rescue experiments Molecular cancer research : MCR Medium 34158392
2022 Sohlh2 functions as a tumor suppressor in renal cell carcinoma by downregulating DNMT3a, leading to demethylation and upregulation of Klotho; Sohlh2 expression positively correlates with Klotho and negatively with DNMT3a. Sohlh2 overexpression/knockdown in RCC lines, Western blot and qPCR for DNMT3a and Klotho, CCK-8 proliferation assay, in vivo xenograft, IHC in patient samples Frontiers in oncology Low 35127476
2023 SOHLH2 overexpression in macrophages promotes M2 polarization by directly binding the LXRα promoter and upregulating LXRα, ABCA1, and ABCG1 expression, disturbing membrane lipid homeostasis; E3 ubiquitin ligase TRIM21 promotes SOHLH2 ubiquitination and proteasomal degradation, suppressing M2 polarization and TNBC progression. Sohlh2 overexpression in macrophages, ChIP/reporter assay for LXRα promoter, co-IP and ubiquitination assay with TRIM21, in vivo lung metastasis model Cell death & disease Medium 38123542
2023 Sohlh2 represses pulmonary fibrosis-associated oxidative stress by directly repressing p62 transcription, thereby inhibiting the p62/Keap1/Nrf2 anti-oxidative signaling pathway; Sohlh2 overexpression increases ROS and apoptosis in alveolar epithelial cells, reversed by the ROS inhibitor NAC. Type II AEC-specific Sohlh2 conditional knock-in mouse, Sohlh2 overexpression in A549 cells, ROS measurement, apoptosis assay, NAC rescue, promoter analysis for p62 Cell death & disease Medium 37875506
2023 Sohlh2 directly binds the LncRNA-H19 promoter and represses its transcription, suppressing colon cancer stem cell stemness and promoting differentiation via the LncRNA-H19/miR-141/β-catenin pathway; LncRNA-H19 mediates Sohlh2 effects on CSC stemness. ChIP and luciferase reporter for H19 promoter, LncRNA-H19 rescue/knockdown epistasis, in vitro and in vivo CSC assays Molecular cancer research : MCR Medium 36287177
2024 SOHLH2 promotes hepatocellular carcinoma progression by directly binding the TGM2 promoter and enhancing its transcriptional activity, thereby promoting autophagy of HCC cells. Sohlh2 overexpression/knockdown in HCC lines, ChIP and reporter assay for TGM2 promoter, in vitro and in vivo proliferation/migration/invasion assays Molecular carcinogenesis Medium 39436118
2026 PRMT5 mediates arginine methylation of SOHLH2 in vascular endothelial cells, promoting CUL4B-mediated ubiquitylation and degradation of SOHLH2; SOHLH2 in turn promotes Sirt1 transcription and represses NF-κB signaling, suppressing endothelial cell senescence, permeability, and TNBC trans-endothelial migration. Tissue microarray, Sohlh2 endothelial-specific knock-in mouse, co-IP for PRMT5-SOHLH2 and CUL4B interactions, ubiquitination assay, ChIP/reporter assay for Sirt1 promoter, in vivo lung metastasis model Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 41867089
2026 SOHLH2 transcriptionally activates RAD54L expression by binding its promoter, promoting homologous recombination repair of DNA double-strand breaks and conferring radioresistance in NSCLC; RAD54L overexpression rescues the suppression of HR repair caused by SOHLH2 knockdown. SOHLH2 overexpression/knockdown in NSCLC cells, ChIP/reporter assay for RAD54L promoter, HR repair assay, RAD54L rescue experiment, in vitro and in vivo radioresistance assays Cell death discovery Medium 41535248

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 SOHLH1 and SOHLH2 coordinate spermatogonial differentiation. Developmental biology 150 22056784
2006 Sohlh2 is a germ cell-specific bHLH transcription factor. Gene expression patterns : GEP 85 16765102
2008 Sohlh2 knockout mice are male-sterile because of degeneration of differentiating type A spermatogonia. Stem cells (Dayton, Ohio) 76 18339773
2008 Sohlh2 affects differentiation of KIT positive oocytes and spermatogonia. Developmental biology 72 19014927
2012 SOHLH1 and SOHLH2 control Kit expression during postnatal male germ cell development. Journal of cell science 71 22328502
2017 Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I. The Journal of clinical investigation 54 28504655
2014 Novel variants in the SOHLH2 gene are implicated in human premature ovarian failure. Fertility and sterility 43 24524832
2023 TRIM21-mediated Sohlh2 ubiquitination suppresses M2 macrophage polarization and progression of triple-negative breast cancer. Cell death & disease 41 38123542
2012 Effects of BMP4/SMAD signaling pathway on mouse primordial follicle growth and survival via up-regulation of Sohlh2 and c-kit. Molecular reproduction and development 35 23212987
2014 BMP4/Smad signaling pathway induces the differentiation of mouse spermatogonial stem cells via upregulation of Sohlh2. Anatomical record (Hoboken, N.J. : 2007) 32 24591295
2011 Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proceedings of the National Academy of Sciences of the United States of America 31 22143754
2011 DNA methylation of germ-cell-specific basic helix-loop-helix (HLH) transcription factors, Sohlh2 and Figlα during gametogenesis. Molecular human reproduction 29 21427160
2014 Sohlh2 inhibits ovarian cancer cell proliferation by upregulation of p21 and downregulation of cyclin D1. Carcinogenesis 28 24858206
2023 Sohlh2 promotes pulmonary fibrosis via repression of p62/Keap1/Nrf2 mediated anti-oxidative signaling pathway. Cell death & disease 22 37875506
2014 Auto-regulation of the Sohlh1 gene by the SOHLH2/SOHLH1/SP1 complex: implications for early spermatogenesis and oogenesis. PloS one 22 25003626
2015 Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9. Molecular carcinogenesis 20 26153894
2014 Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena thermophila telomerase to telomeres. Molecular and cellular biology 18 25225329
2015 SOHLH1 and SOHLH2 directly down-regulate STIMULATED BY RETINOIC ACID 8 (STRA8) expression. Cell cycle (Georgetown, Tex.) 17 25603532
2015 Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3K/Akt/Foxo3a signalling pathway. Reproductive biomedicine online 17 25773528
2019 Sohlh2 inhibits breast cancer cell proliferation by suppressing Wnt/β-catenin signaling pathway. Molecular carcinogenesis 16 30720232
2013 Myb-domain protein Teb1 controls histone levels and centromere assembly in fission yeast. The EMBO journal 15 23314747
2021 SOHLH2 Suppresses Angiogenesis by Downregulating HIF1α Expression in Breast Cancer. Molecular cancer research : MCR 14 34158392
2016 SOHLH2 is essential for synaptonemal complex formation during spermatogenesis in early postnatal mouse testes. Scientific reports 14 26869299
2021 Germline variants at SOHLH2 influence multiple myeloma risk. Blood cancer journal 11 33875642
2015 Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues. PloS one 11 26375665
2014 Association of genetic variants in SOHLH1 and SOHLH2 with non-obstructive azoospermia risk in the Chinese population. European journal of obstetrics, gynecology, and reproductive biology 10 25463635
2020 Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment. Fertility and sterility 8 32690270
2016 Sohlh2 suppresses epithelial to mesenchymal transition in breast cancer via downregulation of IL-8. Oncotarget 8 27384482
2023 Sohlh2 Regulates the Stemness and Differentiation of Colon Cancer Stem Cells by Downregulating LncRNA-H19 Transcription. Molecular cancer research : MCR 7 36287177
2020 Sohlh2 alleviates malignancy of EOC cells under hypoxia via inhibiting the HIF1α/CA9 signaling pathway. Biological chemistry 6 31318683
2022 Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a. Frontiers in oncology 4 35127476
2024 Sohlh2 Promotes the Progression of Hepatocellular Carcinoma via TGM2-Mediated Autophagy. Molecular carcinogenesis 2 39436118
2026 SOHLH2-RAD54L axis induces radioresistance by promoting homologous recombination repair in non-small cell lung cancer. Cell death discovery 0 41535248
2026 Sohlh2 inhibited the angiogenesis of hepatocellular carcinoma through the HIF-1α/VEGFA pathway. Translational oncology 0 41775083
2026 PRMT5/Sohlh2/Sirt1 Signaling Pathway in Vascular Endothelial Cells Modulates Lung Metastasis of Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41867089

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