Affinage

CSE1L

Exportin-2 · UniProt P55060

Length
971 aa
Mass
110.4 kDa
Annotated
2026-06-09
71 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSE1L/CAS is an essential nuclear transport receptor that recycles importin-α from the nucleus to the cytoplasm, a function conserved from the essential yeast CSE1 gene to the human homologue and required for accurate mitotic chromosome segregation (PMID:8336709, PMID:7479798). Structural and mutagenesis work defines the mechanism: cargo-free Cse1 adopts a closed HEAT-repeat ring that occludes RanGTP sites, and cargo binding drives a major conformational change at HEAT repeat 8 that couples importin-α and Ran contacts, with cooperative cNLS-cargo release in the nucleus requiring RanGTP and Nup2 (PMID:15866177, PMID:32734712). This transport activity is biologically central: CSE1L mediates nuclear import of specific repressive cargo (HDAC1/2/8 and NOVA1), and its loss causes cytosolic mislocalization of these factors and genome-wide derepression of methylated genes without changing DNA methylation (PMID:29636421), while also driving nuclear accumulation of the coactivator TAZ/WWTR1 via importin-α5 and influencing RELA localization (PMID:34022224, PMID:33869740). CSE1L is essential for early embryonic development and, cell-autonomously, for neural crest cell survival, where its ablation causes p53 elevation and massive apoptosis (PMID:11564884, PMID:41380931). Beyond transport, CSE1L associates with microtubules and the mitotic spindle and with α/β-tubulin (PMID:8610099, PMID:18377724), participates in pathway-selective apoptosis (PMID:7479798, PMID:8639641), occupies p53 target promoters to control their transcription and local H3K27 methylation (PMID:17719542), and restrains homologous recombination by negatively regulating nuclear RAD51 (PMID:26123175). An ERK-phosphorylated cytoplasmic pool, downstream of Ras, localizes to cytoplasmic vesicles and drives MMP-containing microvesicle biogenesis, secretion, and cancer cell invasion and metastasis (PMID:18597698, PMID:22952058), and a cytoplasmic form negatively regulates CFTR-dependent fluid secretion (PMID:20933420).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Established the foundational role of the gene: the yeast ortholog is essential for accurate mitotic chromosome segregation, placing it in the chromosome segregation pathway.

    Evidence Conditional yeast mutant screen, complementation cloning, gene disruption

    PMID:8336709

    Open questions at the time
    • Molecular mechanism connecting Cse1 to segregation not defined
    • No biochemical activity assigned at this stage
  2. 1995 Medium

    Identified human CSE1L (CAS) as the functional homologue of yeast CSE1 and implicated it in pathway-selective apoptosis, extending the gene's relevance to mammalian cell death.

    Evidence Expression/selection cloning, antisense cDNA knockdown across multiple toxin paradigms

    PMID:7479798 PMID:8639641

    Open questions at the time
    • Selectivity for TNF/toxin pathways over staurosporine/etoposide unexplained mechanistically
    • No direct molecular target of CAS in apoptosis identified
  3. 1997 Medium

    Connected the human protein to the cell cycle: CAS depletion arrests cells at G2/M with elevated cyclin B, mirroring the yeast mitotic phenotype.

    Evidence Antisense CAS cDNA expression, flow cytometry, cyclin B western blot in HeLa

    PMID:9235994

    Open questions at the time
    • Whether the effect is via transport function or a direct cyclin B role unclear
    • Single-lab antisense approach
  4. 1996 Medium

    Localized CAS to microtubules and the mitotic spindle, providing a cytoskeletal context distinct from its later-defined transport role.

    Evidence Immunofluorescence, cytoskeleton preparations, microtubule drug treatment

    PMID:18377724 PMID:8610099

    Open questions at the time
    • Association is detergent-labile and non-integral; binding partners on the spindle undefined
    • Functional consequence of spindle association for transport unclear
  5. 2001 High

    Demonstrated in vivo essentiality: null knockout causes embryonic lethality by E5.5, showing CSE1L cannot be compensated during early development.

    Evidence Gene targeting in ES cells, mouse knockout, embryo analysis

    PMID:11564884

    Open questions at the time
    • Earliest lethality precludes analysis of later tissue-specific roles
    • Molecular cause of lethality not resolved
  6. 2005 High

    Resolved the structural basis of the transport mechanism: cargo-free Cse1 forms a closed ring that occludes RanGTP, and cargo binding triggers a conformational change coupling importin-α and Ran sites.

    Evidence X-ray crystallography at 3.1 Å, structure comparison, site-directed mutagenesis

    PMID:15866177

    Open questions at the time
    • Structure is of yeast Cse1; human-specific features not addressed
    • Dynamics of the conformational cycle in cells not measured
  7. 2007 High

    Revealed a chromatin/transcriptional role: hCAS/CSE1L occupies p53 target promoters in a p53-autonomous manner and controls their transcription and local H3K27 methylation.

    Evidence ChIP, siRNA knockdown, transcription assays, histone methylation analysis

    PMID:17719542

    Open questions at the time
    • How a transport receptor associates with chromatin mechanistically unclear
    • Link between promoter occupancy and import function not directly tested
  8. 2008 Medium

    Identified PPM1H as a phosphatase that dephosphorylates CSE1L, providing an eraser for CSE1L phosphorylation and a regulatory handle on its activity.

    Evidence Co-IP/mass spectrometry, in vitro phosphatase assay, SDS-PAGE mobility shift

    PMID:18059182

    Open questions at the time
    • Phosphosites on CSE1L not mapped
    • Functional consequence of dephosphorylation for transport vs vesicle roles not defined
  9. 2010 High

    Uncovered non-transport physiological roles in vertebrates: CSE1L negatively regulates CFTR-dependent fluid secretion and associates with E-cadherin in polarized epithelium.

    Evidence Zebrafish forward genetic screen with fluid secretion assays; GST pull-down and Co-IP with E-cadherin

    PMID:20734115 PMID:20933420

    Open questions at the time
    • Mechanism linking CSE1L to CFTR regulation undefined
    • E-cadherin interaction (Low confidence) lacks mutagenesis/reconstitution
  10. 2012 Medium

    Defined the oncogenic cytoplasmic axis: Ras/ERK phosphorylates CSE1L to drive MMP-containing microvesicle biogenesis and metastasis, and AKT controls its nuclear localization to suppress proapoptotic RASSF1C.

    Evidence Ras/ERK and AKT manipulation, vesicle fractionation, MMP secretion and invasion assays, in vivo metastasis models, immunogold EM

    PMID:18597698 PMID:19383891 PMID:22389439 PMID:22952058

    Open questions at the time
    • How phosphorylation switches CSE1L between transport and vesicle functions not resolved
    • Direct CSE1L cargo within microvesicles not fully defined
  11. 2013 Medium

    Linked nuclear CSE1L to invasion through AKT-dependent phospho-RanBP3 accumulation, coupling the transport machinery to a metastatic gene program.

    Evidence AKT inhibition, immunofluorescence, expression profiling after silencing, invasion/motility assays

    PMID:23948303

    Open questions at the time
    • Direct cargo whose import drives the invasion program not pinpointed
    • Single cancer-cell context
  12. 2015 Medium

    Connected CSE1L to genome stability and to signaling crosstalk: it negatively regulates nuclear RAD51 and HR, and it links cAMP/PKA with Ras/ERK signaling.

    Evidence Co-IP, RAD51 focus and HR reporter assays, chromosomal stability assays; shRNA knockdown with pharmacological pathway activation and immunoblotting

    PMID:26123175 PMID:26331446

    Open questions at the time
    • Whether RAD51 regulation reflects nuclear export/import function untested
    • Direct vs indirect control of ERK signaling unclear
  13. 2018 High

    Established the core mechanistic principle behind epigenetic silencing: CSE1L's nuclear import of HDAC1/2/8 and NOVA1 is required to maintain gene silencing, independent of DNA methylation.

    Evidence Genome-wide siRNA screen, reporter assays, DNA methylation analysis, subcellular fractionation, HDAC distribution western blots

    PMID:29636421

    Open questions at the time
    • Why these specific cargoes depend on CSE1L not fully explained
    • Quantitative contribution of each cargo to derepression unresolved
  14. 2021 Medium

    Extended the import-cargo concept to oncogenic transcription factors: CSE1L promotes importin-α5-dependent TAZ nuclear import and influences RELA localization to drive proliferation/invasion.

    Evidence Affinity pull-down, in vitro Co-IP with a small-molecule modulator, fractionation, invasion/motility assays; Co-IP/MS and NF-κB pathway epistasis

    PMID:33869740 PMID:34022224 PMID:34773052

    Open questions at the time
    • Selectivity of CSE1L for specific cargoes mechanistically undefined
    • Telomerase TLC1 import role (Low confidence) shown only in yeast
  15. 2023 Medium

    Tied CSE1L to p53-dependent tumor suppressor pathways: it negatively regulates the RB-DREAM pathway, and its loss is phenocopied by HDAC1/2 inhibition, reinforcing the HDAC-import link.

    Evidence siRNA knockdown, immunoblotting for DREAM components, viability assays, pharmacological HDAC inhibition

    PMID:37759078

    Open questions at the time
    • Direct mechanism connecting CSE1L to RB/p21 unclear
    • Whether effect is purely via HDAC import not isolated
  16. 2025 High

    Demonstrated a cell-autonomous developmental requirement: neural crest-specific ablation causes p53 elevation and apoptosis, and CSE1L participates in cancer protein-stability and adhesion networks (TRIP13, DDX27, FAK).

    Evidence Conditional Cre/lox and CRISPR knockout with histology and p53/apoptosis readouts; Co-IP, ubiquitination assays, RNA-seq, and rescue experiments in cancer models

    PMID:38301874 PMID:39816536 PMID:41260444 PMID:41380931

    Open questions at the time
    • Mechanism linking CSE1L loss to p53 elevation undefined
    • DDX27 and FAK links (Low confidence) lack direct binding/mechanistic detail

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CSE1L phosphorylation by ERK and AKT-controlled localization mechanistically switches the protein between importin-α recycling, chromatin/transcriptional control, and cytoplasmic microvesicle biogenesis remains unresolved.
  • No unified model integrating the transport, vesicular, and transcriptional pools
  • Phosphosite-resolved structure-function mapping in human CSE1L lacking
  • Determinants of cargo selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005576 extracellular region 1
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 1
Partners
E-CADHERINIMPORTIN-ΑPPM1HRAD51RANGTPRELATRIP13WWTR1
Complex memberships
CSE1L–importin-α–RanGTP export complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Yeast CSE1 (ortholog of human CSE1L) is an essential gene required for accurate mitotic chromosome segregation; cse1 mutants accumulate large-budded cells with aberrant binucleate morphologies and show predominantly nondisjunction events, placing Cse1 in the chromosome segregation pathway. Conditional yeast mutant screen, complementation cloning, gene disruption Molecular and cellular biology High 8336709
1995 Human CSE1L (CAS) is the functional homologue of yeast CSE1 (59% overall protein homology, similar length); antisense reduction of CAS protein confers resistance to Pseudomonas exotoxin, diphtheria toxin, and TNF-mediated apoptosis, establishing CAS as a factor in selected apoptotic pathways. Expression/selection cloning, antisense cDNA, cDNA sequence analysis Proceedings of the National Academy of Sciences of the United States of America Medium 7479798
1996 CAS reduction by antisense cDNA confers resistance to TNF-alpha, TNF-beta, Pseudomonas exotoxin, and diphtheria toxin-induced apoptosis but not to staurosporine, cycloheximide, or etoposide, indicating pathway-selective involvement of CAS in apoptosis. Antisense cDNA expression, cell viability and apoptosis assays Biochemistry Medium 8639641
1996 CAS protein localizes to microtubules and the mitotic spindle in proliferating cells; it shows microtubule-like distribution in interphase and labels the mitotic spindle, but is removed by mild detergent treatment and disperses in taxol/vincristine-treated cells, indicating it is associated with but not an integral part of microtubules. Immunofluorescence microscopy, cytoskeleton preparations, drug treatment Proceedings of the National Academy of Sciences of the United States of America Medium 8610099
1997 Antisense-mediated reduction of CAS protein in HeLa cells perturbs G2-to-G1 cell cycle progression and causes G2/M arrest, with elevated cyclin B levels, consistent with a role in mitosis and cyclin B degradation analogous to yeast Cse1. Antisense CAS cDNA expression, flow cytometry, cyclin B western blot Biochemistry Medium 9235994
2001 Homozygous knockout of Cse1l in mice causes embryonic lethality by E5.5, demonstrating that CSE1L is essential for early embryonic development and cannot be compensated by other genes in vivo. Gene targeting in embryonic stem cells, mouse knockout, embryo analysis Molecular and cellular biology High 11564884
2005 Crystal structure of cargo-free yeast Cse1 at 3.1 Å reveals a closed ring conformation formed by N- and C-terminal HEAT-repeat arches; comparison with cargo-bound Cse1 shows a major conformational change at HEAT repeat 8 upon cargo binding, where the insertion connects RanGTP and importin-α contact sites. In the closed state, RanGTP binding sites are occluded and importin-α sites are distorted. Mutations destabilizing the N-to-C interaction uncouple importin-α and Ran binding. X-ray crystallography (3.1 Å), structure comparison, site-directed mutagenesis Molecular cell High 15866177
2007 hCAS/CSE1L associates with a subset of p53 target promoters (including PIG3) in a p53-autonomous manner; its downregulation decreases transcription from those promoters and reduces apoptosis, and its silencing leads to increased methylation of histone H3 lysine 27 at the PIG3 gene, establishing a chromatin regulatory role. ChIP, siRNA knockdown, transcription assays, histone methylation analysis Cell High 17719542
2007 PPM1H (protein phosphatase 1H/PP2C family) physically associates with CSE1L as identified by co-immunoprecipitation/mass spectrometry; PPM1H dephosphorylates CSE1L in vitro and in cells (shown by altered SDS-PAGE mobility), identifying PPM1H as a phosphatase (eraser) for CSE1L phosphorylation. Co-immunoprecipitation/mass spectrometry, in vitro phosphatase assay, SDS-PAGE mobility shift Cancer biology & therapy Medium 18059182
2008 CAS/CSE1L associates with alpha-tubulin and beta-tubulin, enhances tubulin heterodimer association, and its overexpression reduces paclitaxel-induced G2/M arrest and microtubule aster formation while enhancing apoptosis from other chemotherapeutic agents; knockdown produces opposite effects. Co-immunoprecipitation, flow cytometry, immunofluorescence, overexpression/knockdown BMB reports Medium 18377724
2008 CAS/CSE1L overexpression enhances MMP-2 secretion and cancer cell invasion while failing to increase proliferation; CAS localizes to cytoplasmic vesicles and vesicle membranes (immunogold EM); CAS reduction inhibits B16-F10 melanoma metastasis in vivo by 56%. Overexpression/knockdown, Matrigel invasion assay, immunofluorescence, immunogold electron microscopy, animal metastasis model Journal of experimental & clinical cancer research Medium 18597698
2009 CAS/CSE1L co-localizes with MMP-2 in vesicles at the cell membrane exterior; its C-terminal domain associates with MMP-2-containing vesicles; CAS is secreted and detected in conditioned medium and patient sera, establishing CAS as a secretory protein associated with vesicular MMP-2 trafficking. Co-localization (immunofluorescence), vesicle fractionation, immunoblotting of conditioned medium and sera Cancer epidemiology, biomarkers & prevention Medium 19383891
2009 CAS/CSE1L overexpression induces polarization of HT-29 colorectal cells, increases translocation of CAS-stained vesicles to the cell membrane/protrusions, and enhances secretion of CEA and cathepsin D, demonstrating a role in directed epithelial secretion. CAS overexpression, immunofluorescence, ELISA for secreted proteins Molecular and cellular biochemistry Low 19224336
2010 Loss-of-function mutation in zebrafish cse1l causes dramatic fluid accumulation in the gut due to uncontrolled CFTR channel activation; analyses in zebrafish larvae and mammalian cells confirmed that Cse1l is a negative regulator of CFTR-dependent fluid secretion. Forward genetic screen (zebrafish), mutant characterization, fluid secretion assays in zebrafish and mammalian cells Current biology High 20933420
2010 CSE1L associates with E-cadherin in GST pull-down and co-immunoprecipitation experiments; both proteins co-distribute basolaterally in polarized colorectal gland epithelium, linking CSE1L to E-cadherin-mediated epithelial polarity. GST pull-down, co-immunoprecipitation, immunohistochemistry Journal of molecular histology Low 20734115
2012 v-H-Ras expression triggers ERK-dependent phosphorylation of CSE1L and induces microvesicle biogenesis; CSE1L overexpression triggers microvesicle generation; CSE1L knockdown reduces Ras-induced microvesicle biogenesis, MMP-2/MMP-9 secretion, and B16F10 melanoma metastasis, identifying CSE1L as a Ras/ERK-regulated microvesicle membrane protein. Ras overexpression, ERK inhibition, CSE1L knockdown/overexpression, vesicle fractionation, MMP secretion assay, animal metastasis model Molecular medicine Medium 22952058
2012 In ovarian cancer cells, nuclear localization of CSE1L depends on constitutively active AKT; AKT inactivation translocates CSE1L to the cytoplasm, and expression of constitutively active AKT forces cytoplasmic CSE1L into the nucleus. Nuclear CSE1L transcriptionally suppresses the proapoptotic RASSF1C gene, mediating ovarian cancer cell survival. AKT inhibition/activation, immunofluorescence, RNA interference, apoptosis assays, gene expression analysis FASEB journal Medium 22389439
2013 AKT-driven nuclear localization of CSE1L in ovarian cancer cells is associated with nuclear accumulation of phosphorylated RanBP3 (also AKT-dependent); nuclear CSE1L is required for expression of invasion/metastasis-promoting genes and for cell motility and invasiveness. AKT inhibition, immunofluorescence, expression profiling after CSE1L silencing, invasion/motility assays Experimental cell research Medium 23948303
2015 hCAS/CSE1L associates with RAD51 in human cells; under normal conditions, hCAS/CSE1L negatively regulates nuclear RAD51 levels and represses DNA damage-induced RAD51 focus formation and homologous recombination (HR) activity, thereby controlling chromosome stability. Co-immunoprecipitation, siRNA knockdown, RAD51 focus formation assay, HR reporter assay, chromosomal stability assay Genes to cells Medium 26123175
2015 CSE1L regulates Ras-induced ERK1/2 phosphorylation and links cAMP/PKA and Ras/ERK pathways; IBMX (cAMP/PKA activator) induces CSE1L phosphorylation and augments Ras-induced ERK1/2 phosphorylation; CSE1L knockdown inhibits Ras-induced ERK1/2, phospho-CREB, MITF, and tyrosinase expression in melanoma cells. CSE1L shRNA knockdown, pharmacological pathway activation, immunoblotting Molecular carcinogenesis Medium 26331446
2018 CSE1L depletion causes genome-wide derepression of methylated genes without altering DNA methylation; the silencing defect overlaps with that caused by HDAC inhibitors. CSE1L depletion mislocalizes HDAC1, HDAC2, HDAC8, and NOVA1 to the cytosol, demonstrating that CSE1L's nuclear import function for specific cargo proteins is required to maintain epigenetic gene silencing. Genome-wide siRNA screen, reporter gene assay, DNA methylation analysis, subcellular fractionation, western blot for nuclear/cytoplasmic HDAC distribution Proceedings of the National Academy of Sciences of the United States of America High 29636421
2019 CSE1L silencing in gastric cancer cells decreases MITF expression and consequently reduces GPNMB expression, thereby regulating PI3K/Akt/mTOR and MEK/ERK signaling; GPNMB overexpression rescues the anti-tumor effects of CSE1L inhibition, establishing a CSE1L→MITF→GPNMB→PI3K-Akt/MEK-ERK axis. shRNA knockdown, overexpression rescue, immunoblotting, proliferation/invasion/apoptosis assays Journal of cellular physiology Medium 31347172
2020 In yeast, Cse1 and Nup2 function in concert with RanGTP to mediate cNLS-cargo release in the nucleus; reversing the charge of key residues in importin-α (Arg44) or Cse1 (Asp220) abolishes complex formation both in vitro and in vivo; Nup2 N-terminal basic residues are required for importin-α interaction and Nup2 function, establishing a mechanistic model of cooperative importin-α recycling. Structure-guided mutagenesis, in vitro binding assay, in vivo yeast functional assay, complex formation analysis Traffic High 32734712
2021 CSE1L promotes nuclear accumulation of the transcriptional coactivator TAZ (WWTR1) by facilitating importin-α5-dependent nuclear import; in vitro Co-IP shows a compound (TI-4) strengthens CSE1L–importin-α5 interaction and blocks importin-α5 binding to TAZ. CSE1L silencing delays TAZ nuclear import, and TAZ silencing attenuates CSE1L-promoted colony formation, motility, and invasiveness. Affinity bead pull-down, in vitro co-immunoprecipitation, overexpression/silencing, subcellular fractionation, invasion/motility assays The Journal of biological chemistry Medium 34022224
2021 CSE1L interacts with RELA (p65) by co-immunoprecipitation/mass spectrometry and affects its nuclear localization; CSE1L promotes NSCLC cell proliferation and inhibits apoptosis through activation of the NF-κB/MAPK signaling pathway. Immunoprecipitation/mass spectrometry, gain- and loss-of-function experiments, in vitro and in vivo tumor models, pathway analysis Molecular therapy oncolytics Medium 33869740
2022 PHY34 treatment identifies CAS/CSE1L (via chemoproteomics pulldown) as a target in the nucleocytoplasmic transport pathway; CAS overexpression reduces PHY34-induced apoptosis; PHY34 also inhibits ATP6V0A2 (V-ATPase subunit) to block late-stage autophagy, while simultaneously altering CSE1L-dependent nuclear cargo localization. Mass spectrometry-based chemoproteomics pulldown, CAS overexpression, Annexin V/PARP cleavage apoptosis assays, ATP6V0A2 mutant cell lines Cell death & disease Medium 35013112
2023 CSE1L is a negative regulator of the RB-DREAM pathway; CSE1L knockdown in p53 wild-type NSCLC cells increases p21, activates RB1 and RBL2, and represses DREAM target genes, inducing toxicity in a p53-dependent manner; this effect can be phenocopied by the HDAC1/2 inhibitor mocetinostat. siRNA knockdown, immunoblotting for DREAM pathway components, cell viability assays, pharmacological HDAC inhibition Scientific reports Medium 37759078
2021 In zebrafish/yeast, Cse1 (yeast ortholog) participates in TLC1 telomerase RNA import into the nucleus and Sm-ring stabilization on TLC1; Cse1 mutation leads to Y' element amplification and elongated telomere ends, identifying Cse1 as a quality control factor in telomerase maturation. Yeast genetics, RNAi, telomere southern blot, RNA import assay Scientific reports Low 34773052
2024 CSE1L physically interacts with DDX27 (Co-IP confirmed) in oral cancer cells and acts as a downstream effector; CSE1L silencing impairs cell growth promoted by DDX27 overexpression, establishing CSE1L as a downstream target in the DDX27 oncogenic axis. Co-immunoprecipitation, shRNA knockdown, cell rescue experiments Life sciences Low 38301874
2024 CSE1L upregulates the focal adhesion pathway and p-FAK (Y397) in gastric cancer cells; CSE1L knockout reduces p-FAK(Y397) levels and enhances sensitivity to the FAK inhibitor defactinib, identifying CSE1L as a regulator of FAK phosphorylation. CSE1L knockout and overexpression, RNA-seq pathway analysis, western blot, immunofluorescence, drug sensitivity assay Translational cancer research Low 39816536
2025 CSE1L interacts with TRIP13 (co-immunoprecipitation); CSE1L represses TRIP13 ubiquitination-dependent degradation, stabilizing TRIP13 expression, while TRIP13 reciprocally regulates CSE1L protein stability, forming a bidirectional regulatory loop that promotes gastric cancer progression. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, in vitro and in vivo tumor models International journal of biological macromolecules Medium 41260444
2025 Conditional neural crest-specific ablation of Cse1l (Wnt1-Cre2; Cse1l) causes severe forebrain/midbrain/hindbrain malformations, craniofacial hypoplasia, embryonic lethality by E11.5 from ventricular myocardium defects, and dramatically increased apoptosis with elevated p53 expression at E9.5, establishing a cell-autonomous requirement for CSE1L in neural crest cell survival. Conditional Cre/lox knockout, CRISPR-Cas9 null allele generation, histology, immunofluorescence for apoptosis and p53 Developmental biology High 41380931

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1. Proceedings of the National Academy of Sciences of the United States of America 162 7479798
2007 hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes. Cell 153 17719542
1993 CSE1 and CSE2, two new genes required for accurate mitotic chromosome segregation in Saccharomyces cerevisiae. Molecular and cellular biology 116 8336709
2003 CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis : an international journal on programmed cell death 101 12510150
1996 Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. Biochemistry 78 8639641
2005 The structure of the nuclear export receptor Cse1 in its cytosolic state reveals a closed conformation incompatible with cargo binding. Molecular cell 58 15866177
2012 CSE1L, a novel microvesicle membrane protein, mediates Ras-triggered microvesicle generation and metastasis of tumor cells. Molecular medicine (Cambridge, Mass.) 55 22952058
1996 The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle. Proceedings of the National Academy of Sciences of the United States of America 55 8610099
2012 A natural product inspired tetrahydropyran collection yields mitosis modulators that synergistically target CSE1L and tubulin. Angewandte Chemie (International ed. in English) 51 23080551
2010 Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis. Journal of experimental & clinical cancer research : CR 51 20701792
2010 Cse1l is a negative regulator of CFTR-dependent fluid secretion. Current biology : CB 44 20933420
2001 High expression of the proliferation and apoptosis associated CSE1L/CAS gene in hepatitis and liver neoplasms: correlation with tumor progression. International journal of molecular medicine 44 11295109
2008 CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells. Journal of experimental & clinical cancer research : CR 42 18597698
2013 MIR-137 suppresses growth and invasion, is downregulated in oligodendroglial tumors and targets CSE1L. Brain pathology (Zurich, Switzerland) 41 23252729
2001 Implication of the proliferation and apoptosis associated CSE1L/CAS gene for breast cancer development. Anticancer research 38 11724300
2016 CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 27596143
2012 Cellular apoptosis susceptibility (chromosome segregation 1-like, CSE1L) gene is a key regulator of apoptosis, migration and invasion in colorectal cancer. The Journal of pathology 36 22450763
2001 Cse1l is essential for early embryonic growth and development. Molecular and cellular biology 35 11564884
2008 CSE1L/CAS, a microtubule-associated protein, inhibits taxol (paclitaxel)-induced apoptosis but enhances cancer cell apoptosis induced by various chemotherapeutic drugs. BMB reports 33 18377724
2012 CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression. Cellular oncology (Dordrecht, Netherlands) 32 22711543
2022 PHY34 inhibits autophagy through V-ATPase V0A2 subunit inhibition and CAS/CSE1L nuclear cargo trafficking in high grade serous ovarian cancer. Cell death & disease 31 35013112
2019 CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF. Journal of cellular physiology 31 31347172
2018 Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing. Proceedings of the National Academy of Sciences of the United States of America 28 29636421
2012 The cellular apoptosis susceptibility CAS/CSE1L gene protects ovarian cancer cells from death by suppressing RASSF1C. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 22389439
2013 Suppression of cellular apoptosis susceptibility (CSE1L) inhibits proliferation and induces apoptosis in colorectal cancer cells. Asian Pacific journal of cancer prevention : APJCP 27 23621178
2016 Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro. The American journal of pathology 26 27521996
2009 Higher prevalence of secretory CSE1L/CAS in sera of patients with metastatic cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 26 19383891
1997 Antisense inhibition of CAS, the human homologue of the yeast chromosome segregation gene CSE1, interferes with mitosis in HeLa cells. Biochemistry 26 9235994
2020 Circ_cse1l Inhibits Colorectal Cancer Proliferation by Binding to eIF4A3. Medical science monitor : international medical journal of experimental and clinical research 25 32857753
2015 CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells. Molecular carcinogenesis 24 26331446
2007 Protein phosphatase 1H, overexpressed in colon adenocarcinoma, is associated with CSE1L. Cancer biology & therapy 24 18059182
2013 AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells. Experimental cell research 23 23948303
2013 Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage. Journal of translational medicine 19 23369209
2009 Function of CSE1L/CAS in the secretion of HT-29 human colorectal cells and its expression in human colon. Molecular and cellular biochemistry 19 19224336
2021 Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway. Molecular therapy oncolytics 18 33869740
2021 CSE1L promotes nuclear accumulation of transcriptional coactivator TAZ and enhances invasiveness of human cancer cells. The Journal of biological chemistry 18 34022224
2018 CSE1L participates in regulating cell mitosis in human seminoma. Cell proliferation 17 30485574
2012 A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome. Annals of oncology : official journal of the European Society for Medical Oncology 17 22967991
2007 Synergic CSE1L/CAS, TNFR-1, and p53 apoptotic pathways in combined interferon-gamma/adriamycin-induced apoptosis of Hep G2 hepatoma cells. Journal of experimental & clinical cancer research : CR 16 17550137
2013 CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression. American journal of surgery 15 23806821
2015 Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts. Journal of translational medicine 13 26070816
2020 CSE1L promotes proliferation and migration in oral cancer through positively regulating MITF. European review for medical and pharmacological sciences 12 32495878
2020 Dissecting the roles of Cse1 and Nup2 in classical NLS-cargo release in vivo. Traffic (Copenhagen, Denmark) 12 32734712
2015 hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair. Genes to cells : devoted to molecular & cellular mechanisms 12 26123175
2022 Interfering with CSE1L/CAS inhibits tumour growth via C3 in triple-negative breast cancer. Cell proliferation 11 35403306
2015 The relationship between CSE1L expression and axillary lymph node metastasis in breast cancer. Tumori 11 25791533
1999 Tissue-specific alternative splicing of the CSE1L/CAS (cellular apoptosis susceptibility) gene. Genomics 11 10331944
2021 CSE1L silencing impairs tumor progression via MET/STAT3/PD-L1 signaling in lung cancer. American journal of cancer research 10 34659893
2015 Does CSE1L Overexpression Affect Distant Metastasis Development in Breast Cancer? Oncology research and treatment 10 26278417
2010 Differential distributions of CSE1L/CAS and E-cadherin in the polarized and non-polarized epithelial glands of neoplastic colorectal epithelium. Journal of molecular histology 10 20734115
2004 CSE1/CAS overexpression inhibits the tumorigenicity of HT-29 colon cancer cells. Journal of experimental & clinical cancer research : CR 10 15354419
2015 High expression of cytoplasmic phosphorylated CSE1L in malignant melanoma but not in benign nevi: phosphorylated CSE1L for the discrimination between melanoma and benign nevi. International journal of clinical and experimental pathology 9 25973023
2024 DDX27 regulates oral squamous cell carcinoma development through targeting CSE1L. Life sciences 8 38301874
2012 Presence of CSE1L protein in urine of patients with urinary bladder urothelial carcinomas. The International journal of biological markers 8 22653741
2023 CSE1L is a negative regulator of the RB-DREAM pathway in p53 wild-type NSCLC and can be targeted using an HDAC1/2 inhibitor. Scientific reports 7 37759078
2023 The role of CSE1L silencing in the regulation of proliferation and apoptosis via the AMPK/mTOR signaling pathway in chronic myeloid leukemia. Hematology (Amsterdam, Netherlands) 6 36652402
2021 Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint. Scientific reports 6 34773052
2018 Expression of CAS/CSE1L, the Cellular Apoptosis Susceptibility Protein, Correlates With Neoplastic Progression in Barrett's Esophagus. Applied immunohistochemistry & molecular morphology : AIMM 6 27941559
2014 Crystal structure of Thermobifida fusca Cse1 reveals target DNA binding site. Protein science : a publication of the Protein Society 6 25420472
2023 Aberrantly Expressed Hsa_circ_0060762 and CSE1L as Potential Peripheral Blood Biomarkers for ALS. Biomedicines 5 37238987
2019 The role of CSE1L expression in cervical lymph node metastasis of larynx tumors. Brazilian journal of otorhinolaryngology 4 31383592
2021 A Novel Mutation in Cse1l Disrupts Brain and Eye Development with Specific Effects on Pax6 Expression. Journal of developmental biology 3 34287339
2019 Functional regulation of human trophoblast cells by CSE1L. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 3 31394954
2024 CSE1L in enhancing the effect of defactinib on gastric cancer cells via the inhibition of FAK phosphorylation. Translational cancer research 2 39816536
2022 Role of CSE1L expression in determining recurrence and survival of laryngeal tumors. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 2 35137271
2023 The nuclear transport factor CSE1 drives macronuclear volume increase and macronuclear node coalescence in Stentor coeruleus. iScience 1 37520736
2025 Cse1l Regulates Neural Crest Cell Survival and is Critical for Craniofacial and Cardiac Development. bioRxiv : the preprint server for biology 0 40654873
2025 Novel e4a2 BCR∷ABL1 transcript with insertion of CSE1L exons 9 and 10 in a CML patient: a case report. Frontiers in oncology 0 40881880
2025 CSE1L regulates gastric cancer progression via molecular crosstalk with TRIP13. International journal of biological macromolecules 0 41260444
2025 Cse1l is critical for cell survival, craniofacial and cardiac development. Developmental biology 0 41380931
2024 CSE1L Silencing Enhances Cytarabine-mediated Cytotoxicity in Acute Myeloid Leukemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 0 39469152

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