| 2013 |
KPNB1 is the major importin β receptor mediating NF-κB/p65 nuclear import in a NLS-dependent manner following TNF-α stimulation, acting via the canonical KPNA2/KPNB1 pathway; siRNA knockdown of KPNB1 reduced nuclear p65 and decreased NF-κB transcriptional activity. |
High-content siRNA screening of 17 importin β family members, followed by nuclear fractionation and reporter assays |
Traffic (Copenhagen, Denmark) |
High |
23906023
|
| 2015 |
KPNB1 mediates nuclear translocation of PER proteins (and the PER/CRY repressor complex) in a circadian fashion and independently of importin α, thereby enabling negative feedback regulation of the mammalian circadian clock; RNAi depletion of KPNB1 traps PER/CRY in the cytoplasm and disrupts clock function. |
RNAi knockdown in human cells with cytoplasmic/nuclear fractionation and co-immunoprecipitation; inducible inhibition of Drosophila importin β in lateral neurons abolished behavioral rhythms |
eLife |
High |
26319354
|
| 2014 |
EZH2 epigenetically suppresses miR-30d transcription, which relieves repression of KPNB1 (miR-30d targets KPNB1 3′ UTR), resulting in elevated KPNB1 that promotes MPNST cell survival; forced KPNB1 overexpression rescues apoptosis induced by EZH2 knockdown, placing KPNB1 downstream of the EZH2-miR-30d axis. |
Genetic epistasis: EZH2 knockdown, miR-30d overexpression, KPNB1 overexpression rescue; 3′ UTR luciferase reporter assay; xenograft tumor model |
The Journal of pathology |
High |
24132643
|
| 2015 |
miR-30a also targets the KPNB1 3′ UTR in MPNST cells, contributing to EZH2/miR-30a,d/KPNB1 signaling axis; pharmacological EZH2 inhibition (DZNep) downregulates KPNB1 protein and suppresses tumor growth. |
3′ UTR luciferase reporter assay; Western blot; xenograft mouse model with IHC |
Molecular cancer |
Medium |
25890085
|
| 2017 |
KPNB1 acts as a master regulator of cell cycle-related proteins (including p21, p27, and APC/C); genetic and pharmacological inhibition of KPNB1 causes multiphase cell cycle arrest and apoptosis induction in epithelial ovarian cancer cells in vitro and in vivo. |
shRNA dropout screen in xenografts, CRISPR/Cas9 genome-wide screen, pharmacological inhibition, proteomics |
Proceedings of the National Academy of Sciences of the United States of America |
High |
28811376
|
| 2017 |
KPNB1 is required for translocation of NF-κB and AP-1 transcription factors into the nucleus in cervical cancer cells; siRNA or small-molecule inhibition of KPNB1 (INI-43) causes cytoplasmic retention of NF-κB and decreases AP-1 transcriptional activity, reducing expression of IL-6, IL-1β, TNF-α, and GM-CSF, and impairing cancer cell migration and invasion. |
siRNA knockdown; small-molecule inhibition with INI-43; nuclear fractionation; transcriptional reporter assays; Transwell migration/invasion assays |
Oncotarget |
Medium |
28427184
|
| 2018 |
KPNB1 inhibition in glioblastoma cells causes cytosolic retention of cargo proteins, elevated polyubiquitination, aggresome-like-induced structure (ALIS) formation, and unfolded protein response (UPR) activation; chronic UPR (eIF2α/ATF4 cascade) upregulates pro-apoptotic Bcl-2 family members Puma and Noxa, frees Bax/Bak from Mcl-1, and induces MOMP and apoptosis. |
siRNA knockdown; pharmacological inhibition; Western blot for ubiquitination and UPR markers; rescue by KPNB1 overexpression or protein synthesis inhibitors; combination with proteasome/autophagy inhibitors |
Oncogene |
High |
29520102
|
| 2019 |
KPNB1 inhibition in glioblastoma potentiates TRAIL-induced apoptosis via UPR-mediated ATF4 upregulation of DR5 and 4E-BP1 (suppressing cap-dependent translation of FLIPL/FLIPS), freeing Bax/Bak from Mcl-1, and promoting DISC assembly; KPNB1 inhibition-induced autophagy counteracts by degrading cleaved caspase-8. |
Genetic (siRNA) and pharmacological KPNB1 inhibition; caspase activity assays; Western blot for DISC components; autophagy flux inhibitors |
Cell death & disease |
Medium |
30742128
|
| 2019 |
KPNB1 mediates nuclear import of E2F1 in CML cells; KPNB1 inhibition (siRNA or importazole) blocks E2F1 nuclear translocation, reduces c-Myc and KPNA2 expression downstream of E2F1, and induces G2/M arrest and apoptosis. |
siRNA knockdown; pharmacological inhibition (importazole); immunofluorescence for E2F1 localization; Western blot for E2F1 targets; flow cytometry |
OncoTargets and therapy |
Medium |
31819526
|
| 2020 |
KPNB1 facilitates nuclear translocation of PD-L1 in NSCLC cells; nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, drives Gas6 mRNA synthesis and secretion, activating MerTK signaling to promote cancer cell proliferation. |
Co-immunoprecipitation (KPNB1-PD-L1 binding); nuclear fractionation; PD-L1 knockdown; ChIP for Sp1/nPD-L1 on Gas6 promoter; in vitro and in vivo proliferation assays |
Cell death and differentiation |
Medium |
33139930
|
| 2021 |
KPNB1 mediates nuclear import of IRF1 following ionizing radiation; KPNB1 inhibitor importazole reduces both IRF1 protein upregulation and its nuclear localization, thereby attenuating radiation-increased PD-L1 surface expression on tumor cells. |
siRNA knockdown of IRF1; pharmacological KPNB1 inhibition (importazole); immunofluorescence and Western blot for IRF1 nuclear localization; flow cytometry for surface PD-L1 |
Current issues in molecular biology |
Medium |
34069326
|
| 2022 |
KPNB1 mediates nuclear import of NFAT5 via direct interaction with a unique NFAT5 nuclear localization signal (NFAT5-NLS), independently of karyopherin α; siRNA screening showed only KPNB1 (not karyopherin α) is required for tonicity-responsive NFAT5 nuclear import. |
siRNA screening of importin family; Co-IP; nuclear fractionation; NLS mutagenesis |
Journal of cell science |
High |
35635291
|
| 2022 |
KPNB1 directly interacts with both wild-type and polyQ-expanded ataxin-3 but modulating KPNB1 does not alter ataxin-3 intracellular localization; instead, KPNB1 overexpression reduces ataxin-3 protein levels and aggregate load via protein fragmentation dependent on mitochondrial protease CLPP, improving cell viability in MJD models. |
Co-immunoprecipitation; label-free quantitative proteomics; KPNB1 knockdown/overexpression; CLPP knockdown; MJD mouse model and iPSC analysis |
Cellular and molecular life sciences : CMLS |
Medium |
35794401
|
| 2022 |
PCDH1 interacts with KPNB1 and enhances p65 nuclear localization, thereby activating NF-κB signaling to promote pancreatic ductal adenocarcinoma progression. |
Co-immunoprecipitation (PCDH1-KPNB1); nuclear fractionation of p65; NF-κB reporter assay; cell proliferation/invasion assays |
Cell death & disease |
Medium |
35864095
|
| 2024 |
USP7 stabilizes KPNB1 through deubiquitination (K48-linked ubiquitination removal); KPNB1 mediates nuclear import of transcription factor YBX1, which then binds the NLGN3 promoter to drive NLGN3 expression and promote glioblastoma progression. |
Ubiquitination assays; Co-IP/mass spectrometry (KPNB1-YBX1 interaction); nuclear-cytoplasmic fractionation; immunofluorescence; ChIP for YBX1 on NLGN3 promoter; intracranial tumor model |
Journal of experimental & clinical cancer research : CR |
High |
38254206
|
| 2024 |
TMEM209 binds to KPNB1 and competitively blocks the interaction between KPNB1 and E3 ubiquitin ligase RCHY1, preventing K48-linked ubiquitination-dependent degradation of KPNB1; stabilized KPNB1 then activates the Wnt/β-catenin signaling pathway to promote hepatocellular carcinoma progression. |
Co-immunoprecipitation (TMEM209-KPNB1 and KPNB1-RCHY1); ubiquitination assays; Western blot; xenograft tumor model |
Cell death discovery |
Medium |
39414762
|
| 2024 |
KPNB1 specifically recognizes amino acids 280-299 within the NLS of transcription factor ATF4, mediating ATF4 nuclear import; nuclear ATF4 then binds the BNIP3 promoter (at approximately -1292 to -1279 bp and -1185 to -1172 bp) to drive BNIP3-dependent mitophagy and promote odontoblastic differentiation of dental pulp stem cells. |
IP-mass spectrometry (KPNB1-ATF4); NLS wild-type/mutant plasmid constructs; dual-luciferase reporter and ChIP for ATF4-BNIP3 promoter; nuclear fractionation; mitochondrial function assays; in vivo implantation model |
Cellular & molecular biology letters |
High |
39604846
|
| 2025 |
KPNB1 directly transports VCP (valosin-containing protein) into the nucleus to support DNA damage repair; withaferin A (WA) covalently binds CYS 158 of KPNB1 to retard VCP nuclear localization and impair DDR. |
Chemical pulldown combined with immunoprecipitation-mass spectrometry; biochemical Co-IP; covalent binding site mapping (CYS 158 mutagenesis); in vivo xenograft DDR assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
40339118
|
| 2025 |
KPNB1 mediates nuclear import of HMGB2 in AML cells; KPNB1 inhibition impairs HMGB2 nuclear entry, leading to compromised DNA damage repair and sensitization of AML cells to venetoclax. |
Co-immunoprecipitation; nuclear fractionation; siRNA/importazole inhibition; xenograft AML mouse model; patient-derived cell viability assays |
Oncogene |
Medium |
40082556
|
| 2023 |
RTEL1 interacts with KPNB1 through a distinct C-terminal domain (separate from its NUP153-binding domain), and this interaction connects protein nuclear import to nuclear envelope stability during S-phase; overexpression of the RTEL1 C-terminal domain protects against nuclear envelope anomalies caused by protein import inhibition. |
Co-immunoprecipitation; domain deletion/truncation mapping; high-resolution microscopy (KPNB1 localization at nuclear pore); nuclear envelope stability assays |
Cells |
Medium |
38132118
|
| 2020 |
NLS-RARα is transported into the nucleus by binding to both KPNA2 (importin α1) and KPNB1 (importin β1); knockdown of KPNA2/KPNB1 inhibits nuclear accumulation of NLS-RARα, and nuclear NLS-RARα inhibits myeloid cell differentiation. |
Mass spectrometry of co-immunoprecipitated proteins; Co-IP validation; siRNA knockdown; nuclear/cytoplasmic fractionation; immunofluorescence |
Xi bao yu fen zi mian yi xue za zhi |
Medium |
32696739
|
| 2025 |
KPNB1 is identified as a reader protein for O-GlcNAcylated RNA Polymerase II CTD (at Ser-5); OGT-mediated O-GlcNAcylation of RNA Pol II promotes its nuclear entry in a KPNB1-dependent manner, connecting metabolic state to global transcription regulation. |
WGA lectin pulldown combined with mass spectrometry (O-GlcNAcylated CTD interactome); structural modeling; ChIP (wChIP technique); siRNA/inhibitor functional assays |
bioRxivpreprint |
Medium |
|
| 2025 |
KPNA2/KPNB1 complex sequesters C9orf72 poly(proline-arginine) (polyPR) in the cytoplasm, protecting cells from polyPR nuclear toxicity; genetic silencing of KPNB1 converts PR20-resistant cells to sensitive cells, and KPNB1 overexpression rescues JQ1-induced PR20 nuclear entry and cell death. |
FITC-labeled PR20 tracking; siRNA knockdown of KPNB1/KPNA2; overexpression rescue; JQ1-mediated KPNB1 downregulation |
Cell biochemistry and function |
Medium |
39891383
|
| 2024 |
NAT10 upregulates KPNB1 expression through ac4C RNA modification of KPNB1 mRNA; elevated KPNB1 in turn facilitates PD-L1 nuclear translocation to promote immune escape and radiotherapy resistance in NSCLC. |
NAT10 knockdown; ac4C RNA modification assays; KPNB1 overexpression; nuclear fractionation for PD-L1; immune cell co-culture assays |
Open life sciences |
Low |
40109769
|