| 2017 |
NAP1L1 enhances CSB-mediated nucleosome remodeling by accelerating the activation and translocation phases, and by decreasing pausing probability during translocation, thereby increasing CSB processivity. NAP1L1 also suppresses CSB's non-productive DNA-binding interactions (including gross DNA distortion). |
Single-molecule real-time imaging of nucleosome remodeling; DNA-binding assays with CSB and NAP1L1 |
Nucleic acids research |
High |
28369616
|
| 2018 |
Nap1l1 knockdown in mouse embryos decreases neural progenitor cell (NPC) proliferation and induces premature neuronal differentiation during cortical development. Nap1l1 promotes SETD1A-mediated H3K4 trimethylation at the RassF10 promoter to upregulate RassF10 expression, and RassF10 overexpression rescues the Nap1l1 KO differentiation defect. |
In utero electroporation knockdown; CRISPR-Cas9 knockout mice; RNA-seq; ChIP for H3K4me3 at RassF10 promoter; rescue by RassF10 overexpression |
Cell reports |
High |
29490266
|
| 2017 |
HCV NS5A interacts with NAP1L1, sequesters it in the cytoplasm blocking its nuclear translocation, and NS5A from genotype 2 (but not genotype 1) additionally targets NAP1L1 for proteasome-mediated degradation. NAP1L1 depletion reduces RELA protein levels and strongly impairs IRF3 TBK1/IKKε-mediated phosphorylation, leading to defective RIG-I and TLR3 antiviral responses. |
Co-IP mapping NS5A–NAP1L1 interaction; immunofluorescence for subcellular localization; proteasome inhibitor rescue; siRNA knockdown of NAP1L1 followed by IRF3 phosphorylation and RELA level assays |
Journal of virology |
High |
28659470
|
| 2014 |
NAP1L1 binds directly to the p57(Kip2) promoter region (-164 to +21) and promotes its methylation; NAP1L1 silencing decreases p57(Kip2) promoter methylation, upregulates p57(Kip2) transcript and protein, inhibits mTOR pathway phosphorylation, reduces pancreatic NEN cell proliferation in vitro, and decreases tumor size in an orthotopic mouse model. |
siRNA/shRNA knockdown; chromatin immunoprecipitation (ChIP) at p57(Kip2) promoter; promoter methylation assay; Western blot for mTOR pathway; orthotopic xenograft model |
Epigenetics & chromatin |
High |
25071868
|
| 2019 |
NAP1L1 knockdown decreases p53 Lys320 acetylation under normal conditions (attenuating p21 expression and facilitating cell growth), while under genotoxic stress NAP1L1 knockdown increases p53 Lys382 acetylation (enhancing proapoptotic Bax levels and facilitating cell death). Thus NAP1L1 selectively modulates site-specific p53 acetylation to determine cell fate. |
siRNA knockdown of NAP1L1 and NAP1L4; Western blot for acetylated p53 at Lys320 and Lys382; p21 and Bax expression assays; cell growth and apoptosis assays under normal and genotoxic stress conditions |
Biochimica et biophysica acta. Molecular cell research |
Medium |
31634504
|
| 2016 |
KSHV LANA associates with NAP1L1 via its amino-terminal domain in KSHV-infected cells, recruits NAP1L1 to the terminal repeat (TR) region of the viral genome, and this interaction stimulates LANA-mediated DNA replication and TR plasmid persistence. NAP1L1 depletion reduces nucleosome positioning on the viral genome and increases transcription of viral lytic genes. |
Co-IP; ChIP from NAP1L1-depleted cells; TR-containing plasmid replication assay; nucleosome positioning assay; reporter assay for LANA-regulated promoters |
Scientific reports |
Medium |
27599637
|
| 2021 |
NAP1L1 interacts with HDGF at the protein level and they co-localize in the cytoplasm; HDGF in turn interacts with the transcription factor c-Jun, which induces expression of cell cycle promoters CCND1/CDK4/CDK6, promoting glioma cell proliferation and cisplatin chemoresistance. HDGF knockdown in NAP1L1-overexpressing cells inhibits proliferation. |
Co-IP; immunofluorescence co-localization; siRNA/shRNA knockdown; Western blot for CCND1/CDK4/CDK6; in vitro and in vivo proliferation assays; cisplatin sensitivity assay |
Aging |
Medium |
34959221
|
| 2021 |
NAP1L1 recruits HDGF; HDGF interacts with c-Jun transcription factor to induce CCND1 expression and stimulate HCC cell proliferation. Transfecting HDGF or c-Jun reverses the growth-suppressive effects of NAP1L1 knockdown in HCC cells. |
Co-IP; siRNA/shRNA knockdown; Western blot; in vitro and in vivo proliferation assays; rescue transfection of HDGF/c-Jun |
Frontiers in cell and developmental biology |
Medium |
34368121
|
| 2021 |
NAP1L1 interacts with HDGF (Co-IP and co-localization in cytoplasm), and HDGF recruits c-Jun to induce CCND1 expression and drive proliferation in nasopharyngeal carcinoma. HDGF or c-Jun overexpression rescues growth suppression caused by NAP1L1 knockdown. |
Co-IP; immunofluorescence; siRNA/shRNA knockdown; RNA-seq; GSEA; Western blot; in vitro/in vivo proliferation assays; rescue experiments |
Biomedicine & pharmacotherapy |
Medium |
34563951
|
| 2021 |
NAP1L1 interacts with HDGF (Co-IP, confocal co-localization in cytoplasm); HDGF recruits c-Jun which induces CCND1 expression to drive breast cancer cell proliferation. HDGF overexpression rescues growth suppression from NAP1L1 knockdown. |
Co-IP; confocal immunofluorescence; siRNA/shRNA knockdown; MTT/Edu/colony assays; in vivo xenograft; rescue transfection |
Cancer cell international |
Medium |
34774047
|
| 2022 |
NAP1L1 binds to HDGF, recruits DDX5, and induces β-catenin/CCND1 signaling to promote colon cancer cell proliferation. HDGF or DDX5 overexpression restores cell growth in NAP1L1-knockdown colon cancer cells. |
Co-IP; siRNA knockdown; MTT/EdU/colony assays; in vivo xenograft; rescue transfection; Western blot for β-catenin/CCND1 |
Acta biochimica et biophysica Sinica |
Medium |
36148951
|
| 2022 |
NAP1L1 interacts with HDGF (Co-IP, cytoplasmic co-localization) in ovarian cancer cells; HDGF interacts with c-Jun to induce CCND1 expression and drive cell cycle progression. HDGF overexpression in NAP1L1-knockdown cells reverses proliferation suppression. |
Co-IP; immunofluorescence; siRNA/shRNA knockdown; flow cytometry; cell proliferation assays; rescue experiments |
BMC cancer |
Medium |
35351053
|
| 2021 |
NAP1L1 binding to CHIKV nsP3 hypervariable domain (HVD) requires phosphorylation of HVD by CK2 kinase, and NAP1L1 interacts with two distinct motifs on HVD located upstream and downstream of the G3BP-binding motifs. This NAP1L1–HVD interaction has stimulatory effects on CHIKV replication in vertebrate cells. |
Binding assays mapping interaction to two HVD motifs; phosphorylation requirement demonstrated with CK2 inhibitors/mutants; viral replication assays; mutagenesis of HVD motifs |
Journal of virology |
Medium |
34076483
|
| 2023 |
NAP1L1 is a microtubule-associated protein (MAP): it localizes in the cytosol with microtubules during interphase, binds microtubules through N-terminal (1–72 aa) and central (164–269 aa) regions, dimerizes through a long helix region (73–163 aa), and bundles microtubules in cells. |
Immunofluorescence microscopy of GFP/HA-tagged NAP1L1; co-localization with MTs; in vitro MT-binding assay with bacterially expressed NAP1L1 fragments and purified MTs; MT bundling assay; RNA-seq analysis of NAP1L1-depleted cells |
Cytoskeleton (Hoboken, N.J.) |
Medium |
37098731
|
| 2023 |
MYH9 binds to NAP1L1 and recruits the deubiquitinase USP14, which prevents ubiquitination and proteasomal degradation of NAP1L1. Elevated NAP1L1 in turn binds c-Myc, activates c-Myc, and induces CCND1/CDK4 expression to promote glioma cell proliferation and temozolomide resistance. |
Co-IP; Western blot for ubiquitination; siRNA knockdown of MYH9 and USP14; cell proliferation and drug resistance assays; in vivo experiments |
Cancer cell international |
Medium |
37770914
|
| 2023 |
NAP1L1 binds YAP1 protein and influences its stability; NAP1L1 silencing promotes ubiquitination and proteasomal degradation of YAP1 in cardiac fibroblasts, thereby inhibiting fibroblast proliferation, migration, and differentiation into myofibroblasts. NAP1L1 knockout mice show reduced fibrosis after myocardial infarction. |
Co-IP for NAP1L1–YAP1 interaction; ubiquitination assay; siRNA/shRNA knockdown; NAP1L1 KO mice with MI model; TGF-β1 stimulation assays; Western blot |
MedComm |
Medium |
37593048
|
| 2025 |
The somatic variant NAP1L1 p.D349E destabilizes nucleosome formation, causing cytoplasmic DNA leakage that activates the cGAS-STING innate immune pathway, leading to release of inflammatory molecules and cardiac hypertrophy. This mechanism was found in cardiomyocytes of sporadic hypertrophic cardiomyopathy patients. |
Next-generation sequencing identifying somatic variant; in vivo mouse model; in vitro functional analysis of nucleosome stability; cGAS-STING pathway activation assays |
Nature communications |
Medium |
40169585
|
| 2024 |
FBXW7 (E3 ubiquitin ligase) directly interacts with and ubiquitinates NAP1L1, promoting its proteasomal degradation. Reduced NAP1L1 impairs recruitment of USP14, limiting deubiquitination of HDGF, which in turn suppresses USP14-mediated p62 deubiquitination, leading to autophagy induction and enhanced cisplatin sensitivity in NPC. |
Co-IP; ubiquitination assay; siRNA knockdown; Western blot; autophagy flux assay; in vitro and in vivo cisplatin sensitivity assays; IHC of patient tissues |
Molecular cancer |
Medium |
40414865
|
| 2024 |
NAP1L1 promotes DDX5 transcription by recruiting the acetyltransferase EP300 to the DDX5 promoter, leading to promoter acetylation; DDX5 then activates Wnt/β-catenin signaling by binding β-catenin, promoting endometrial cancer cell proliferation, migration, and invasion. |
ChIP; dual-luciferase reporter assay; Co-IP confirming NAP1L1–EP300 interaction; siRNA/shRNA knockdown; Western blot for Wnt/β-catenin; in vivo xenograft |
Molecular cancer research : MCR |
Medium |
38953887
|
| 2024 |
NAP1L1 does not directly bind BIRC2 (negative result from Co-IP and mass spectrometry). Instead, NAP1L1 protects BIRC2 from ubiquitination and degradation through an intermediate molecule UBR4 (E3 ubiquitin ligase); NAP1L1 knockdown promotes UBR4-mediated ubiquitin degradation of BIRC2, inhibiting HCC cell proliferation and apoptotic escape. |
Co-IP and mass spectrometry (no direct NAP1L1–BIRC2 interaction detected); ubiquitination assay with UBR4 depletion; siRNA knockdown; Western blot; in vitro/in vivo proliferation and apoptosis assays |
Cell death discovery |
Medium |
38538582
|
| 2022 |
NAP1L1 is expressed in human platelets and megakaryocytes. Co-IP experiments reveal that NAP1L1 dynamically interacts with DLAT (PDC-E2), a component of the mitochondrial pyruvate dehydrogenase (PDH) complex. NAP1L1 overexpression in megakaryocytes significantly reduces proplatelet extension formation (thrombopoiesis). PDH activity is increased in platelets from septic patients paralleling NAP1L1 expression levels. |
Co-IP for NAP1L1–PDC-E2 interaction; NAP1L1 overexpression in megakaryocytes with proplatelet formation assay; PDH activity assay in patient platelets; RNAseq |
International journal of molecular sciences |
Medium |
36499021
|
| 2016 |
Nap1l1 overexpression in mouse induced pluripotent stem cells (iPSCs) promotes proliferation and G2/M transition, increases cyclin B1, decreases p21 and p27, and activates AKT and ERK phosphorylation. Inhibition of AKT or ERK signaling suppresses the proliferative effects of Nap1l1 overexpression. |
Lentiviral overexpression and knockdown in iPSCs; MTT assay; flow cytometry for cell cycle; Western blot for cyclin B1, p21, p27, pAKT, pERK; AKT/ERK inhibitor experiments |
Cellular physiology and biochemistry |
Medium |
26824453
|
| 2025 |
The small-molecule inhibitor Z11 (identified by structure-based drug design targeting NAP1L1) interferes with NAP1L1–YAP1 interaction, promoting YAP1 ubiquitination and degradation, thereby inhibiting AKT/mTOR signaling and reducing cardiac fibroblast activation and cardiac fibrosis in TGF-β1 and MI mouse models. |
Structure-based drug design; in vitro TGF-β1 model; in vivo MI mouse model; Western blot for NAP1L1–YAP1 interaction disruption; ubiquitination assay; AKT/mTOR pathway analysis |
European journal of pharmacology |
Low |
41354299
|