| 2001 |
hCAP-H (NCAPH) protein levels remain constant throughout the cell cycle despite cell cycle-restricted transcription (highest in G2); hCAP-H associates with mitotic chromosomes in a non-uniform but symmetric distribution along sister chromatids during mitosis, and localizes to nucleoli during interphase together with hCAP-C and hCAP-E, suggesting condensin associates with rDNA. hCAP-H association with condensed chromatin was not observed in early chromosome condensation when histone H3 phosphorylation has already occurred, consistent with H3 phosphorylation preceding condensin-mediated condensation. |
Cell fractionation, immunofluorescence, in vivo imaging, cell cycle synchronization |
Molecular biology of the cell |
Medium |
11694586
|
| 2005 |
Drosophila CAP-H/Barren (condensin I subunit, ortholog of NCAPH) is required for sister chromatid resolution and for maintaining structural integrity of centromeric and pericentromeric heterochromatin during mitosis. Depletion of Barren/CAP-H causes the condensin core SMC subunits to remain on chromatin while other condensin I non-SMC subunits do not, indicating CAP-H is essential for the association of the non-SMC condensin I subunits with chromosomes. Centromeric heterochromatin assembled without CAP-H cannot withstand mitotic spindle forces and undergoes irreversible distortion after bipolar attachment. |
RNAi depletion in Drosophila S2 cells, immunofluorescence, in vivo live imaging, chromosome fractionation |
Molecular and cellular biology |
High |
16199875
|
| 2010 |
During prolonged mitotic arrest, caspase-3 is activated and cleaves CAP-H (NCAPH), a condensin I subunit. Depletion or cleavage of CAP-H causes loss of condensin I complex from chromosomes, compromising chromosome integrity and facilitating DNA fragmentation by caspase-activated DNase (CAD), thereby driving mitotic death. Expression of a caspase-resistant form of CAP-H abrogates mitotic death and allows cells to re-enter interphase after prolonged mitotic delay. |
Caspase cleavage assay, caspase-resistant mutant expression, immunofluorescence, cell death assays, DNA fragmentation assay |
Cell death and differentiation |
High |
21151026
|
| 2020 |
MYBL2 transcription factor directly binds to the transcription start site (TSS) of NCAPH and upregulates its expression. Overexpression of NCAPH partially rescues cell death and migration blockage induced by MYBL2 knockdown, placing NCAPH downstream of MYBL2 in a proliferation/migration pathway in lung adenocarcinoma cells. |
Chromatin immunoprecipitation (ChIP) assay, siRNA knockdown, rescue overexpression, cell proliferation and migration assays |
Molecular and cellular biochemistry |
Medium |
32200471
|
| 2020 |
HPV E7 upregulates NCAPH expression via E2F1, which binds directly to the NCAPH promoter to initiate transcription. In turn, NCAPH silencing reduces E7 transcription by promoting a shift in the AP-1 heterodimer from c-Fos/c-Jun to Fra-1/c-Jun, establishing a positive feedback loop between E7 and NCAPH. E7-mediated NCAPH overexpression activates the PI3K/AKT/SGK signaling pathway. |
ChIP assay (E2F1 binding to NCAPH promoter), luciferase reporter assay, siRNA knockdown, western blotting, AP-1 transcription factor analysis |
Cell death & disease |
Medium |
33311486
|
| 2022 |
NCAPH interacts with GEN1 (a Holliday junction resolvase) at the N-terminus of NCAPH within chromatin. NCAPH stabilizes GEN1 in chromatin at G2/M phase. DNA inter-strand crosslink (ICL) induction increases expression and interaction of NCAPH and GEN1. NCAPH depletion exacerbates chromosome segregation errors and cytokinesis failure due to sister-chromatid intertwinement. NCAPH resolves DNA-ICL-induced ultra-fine DNA bridges by stabilizing GEN1, thereby ensuring proper chromosome separation and structural stability. |
Co-immunoprecipitation, domain mapping (N-terminus binding), siRNA knockdown, immunofluorescence, chromosome segregation and cytokinesis failure assays, ICL-inducing agent treatment |
Molecules and cells |
Medium |
36380731
|
| 2022 |
NCAPH promotes bladder cancer cell proliferation and inhibits apoptosis through activation of the MEK/ERK signaling pathway. The MEK1/2 inhibitor U0126 blocks the increase in cell proliferation regulated by NCAPH overexpression, confirming pathway dependence. |
Gain- and loss-of-function experiments (overexpression and shRNA knockdown), MEK inhibitor treatment (U0126), western blotting, xenograft mouse model |
Cell cycle (Georgetown, Tex.) |
Medium |
34974790
|
| 2024 |
TRIM21 (an E3 ubiquitin ligase) interacts with NCAPH and ubiquitinates it at the K11 lysine residue, decreasing NCAPH protein stability and promoting its degradation. TRIM21 combines with NCAPH through its PRY/SPRY and CC domains and accelerates NCAPH degradation through its RING domain. TRIM21-mediated NCAPH destabilization promotes autophagosome formation and reduces cell proliferation by suppressing the downstream AKT/mTOR pathway in cervical cancer cells. |
Mass spectrometry, co-immunoprecipitation, domain mutation analysis, ubiquitination assay, western blotting, autophagy assays |
Cell death & disease |
High |
39103348
|
| 2023 |
FOXM1 functions as a transcription factor that directly activates NCAPH expression; FOXM1-mediated NCAPH upregulation promotes colon adenocarcinoma cell stemness and 5-FU resistance via the glycolytic pathway. Inhibition of glycolysis reverses the effect of NCAPH overexpression on stemness and resistance. |
Chromatin immunoprecipitation, dual-luciferase reporter assay, siRNA knockdown, glycolysis assay (Seahorse), sphere formation assay |
Anti-cancer drugs |
Medium |
37260271
|
| 2025 |
NCAPH binds to PD-L1 and disrupts its degradation by competing with HIP1R (Huntingtin-interacting protein 1-related), leading to stabilization of PD-L1 protein and contributing to immunosuppressive tumor microenvironment. A disrupting peptide (NPIDP) that blocks the NCAPH-PD-L1 interaction suppresses tumor immune evasion. Additionally, topotecan (a topoisomerase I inhibitor) binds NCAPH and promotes its proteasomal degradation. |
Co-immunoprecipitation, competition binding assay, peptide disruption experiment, in vitro and in vivo tumor immune evasion assays, proteasomal degradation assay |
Cancer letters |
Medium |
41386505
|
| 2025 |
NCAPH interacts with YAP1 (Hippo pathway effector), promotes LATS1 and YAP1 expression, dephosphorylation, and nuclear translocation, thereby enhancing breast cancer stem cell traits and malignant phenotypes. YAP1 inhibitor Verteporfin reverses NCAPH-driven breast cancer stem cell traits and malignant phenotypes. |
Co-immunoprecipitation, immunofluorescence co-localization, transcriptomic sequencing, GSEA, YAP1 inhibitor functional rescue experiment, in vitro and in vivo assays |
Stem cell research & therapy |
Medium |
40999529
|
| 2025 |
NCAPH regulates E2F1 transcription by binding to the proximal promoter of E2F1 (as shown by ChIP analysis), subsequently stimulating the PI3K/AKT/mTOR pathway and activating downstream targets for cell cycle progression in prostate cancer cells. Combining NCAPH knockdown with mTOR inhibitor (Everolimus) or CDK inhibitor (Flavopiridol) demonstrates synergistic anti-tumor effects in vitro and in vivo. |
Chromatin immunoprecipitation (ChIP), siRNA knockdown, flow cytometry, western blotting, xenograft model, pharmacological inhibitor combination |
International journal of medical sciences |
Medium |
39991770
|
| 2025 |
In vitro reconstitution established that the terminal intrinsically disordered regions (tIDRs) of non-SMC subunits of condensin I suppress its activity, and that Cdk1 phosphorylation relieves this self-suppression. Full activation of condensin I requires phosphorylation of a conserved residue in the central region of the kleisin subunit CAP-H (NCAPH). Conversely, PP2A-B55 induces dissociation of condensin I from reconstituted chromatids, driving their disassembly. The tIDRs and CAP-H central region are phosphorylated and dephosphorylated with distinct kinetics during mitotic entry and exit. |
In vitro reconstitution of mitotic chromatid assembly/disassembly with recombinant proteins, Cdk1/cyclin B phosphorylation assay, PP2A-B55 dephosphorylation assay, Xenopus egg extract complementary analysis, mutagenesis of phosphorylation sites |
bioRxivpreprint |
High |
bio_10.1101_2025.09.08.674995
|