| 2000 |
NRBP1 (NRBP) was identified as a multidomain putative adapter protein containing two putative nuclear receptor binding motifs (LXXLL), a putative SH2 domain-binding region, a kinase-like domain, a bipartite nuclear localization signal, and PEST sequences. In vitro translation revealed three products (60, 51, 43 kDa), suggesting multiple translation initiation sites. |
cDNA cloning, in vitro translation, domain analysis |
Genomics |
Medium |
10843813
|
| 2002 |
NRBP1 physically interacts with activated Rac3 GTPase (constitutively active V12Rac3) and co-localizes with it at endomembranes and lamellipodia. NRBP1 overexpression caused dramatic redistribution of Golgi marker p58, suggesting a role in ER-to-Golgi transport. NRBP contains an associated kinase activity. |
Yeast two-hybrid, co-immunoprecipitation, immunocytochemistry, Golgi redistribution assay |
International journal of molecular medicine |
Medium |
11956649
|
| 2002 |
NRBP1 (Madm) was identified as a binding partner of Mlf1 oncoprotein via yeast two-hybrid; Madm co-immunoprecipitated with Mlf1, co-localized in the cytoplasm, and recruited a serine kinase that phosphorylated both Madm and Mlf1 at the RSXSXP 14-3-3 binding motif. Ectopic Madm expression in M1 myeloid cells suppressed cytokine-induced differentiation. |
Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, ectopic expression/differentiation assay |
The Journal of biological chemistry |
High |
12176995
|
| 2006 |
NRBP1 interacts in vivo with Jab1 (COP9 signalosome component 5) and inhibits Jab1-induced phosphorylation of c-Jun and AP-1 transcriptional activation. Overexpression of NRBP1 specifically inhibits AP-1 activation by various stimuli. |
Co-immunoprecipitation, AP-1 reporter assay, c-Jun phosphorylation assay |
FEBS letters |
Medium |
17052710
|
| 2010 |
Drosophila Madm (NRBP1 ortholog) physically associates with the long TSC22 domain protein Bunched A (BunA) via a conserved motif present only in long TSC22DF isoforms, forming a growth-regulating complex. Genetic and biochemical evidence shows Madm and BunA synergize to promote organ growth. |
Proteomics, co-immunoprecipitation, genetic screen, genetic epistasis, overexpression phenotype |
Journal of biology |
High |
20149264
|
| 2015 |
Drosophila Madm acts downstream of the TOR pathway (epistasis with Tuberous Sclerosis Complex/Rheb) to regulate growth and division of intestinal stem cells; loss of Bunched or Madm suppressed elevated cell growth and 4EBP phosphorylation induced by TSC loss or Rheb overexpression. Bunched (Madm partner) was shown to function in the cytoplasm for this role. |
MARCM clonal analysis, cell-type-specific RNAi, genetic epistasis, 4EBP phosphorylation assay |
Stem cell reviews and reports |
Medium |
26323255
|
| 2016 |
Drosophila Madm acts as a tumour suppressor in testis stem cell competition; Madm knockdown leads to overexpression of EGF receptor ligand vein (vn), activating EGF receptor signalling and integrin expression non-cell-autonomously in cyst stem cells. Constitutively active JAK (hop(Tum-l)) promotes Madm nuclear translocation and suppresses vn/integrin expression. |
RNAi knockdown, genetic epistasis, immunofluorescence (nuclear translocation), EGF receptor signaling assays |
Nature communications |
Medium |
26792023
|
| 2019 |
NRBP1 induces ubiquitination of the stemness transcription factor SALL4, promoting its degradation. THG-1 (a competing binding protein) antagonizes NRBP1 binding to SALL4, preventing SALL4 ubiquitination and stabilizing it to promote stemness gene expression (NANOG, OCT4) and tumorsphere growth in esophageal squamous cell carcinoma cells. |
Co-immunoprecipitation, ubiquitination assay, NRBP1/THG-1 knockdown, tumorsphere assay, rescue experiments |
Biochemical and biophysical research communications |
Medium |
31864704
|
| 2020 |
NRBP1 functions as a substrate receptor of a Cullin-RING ubiquitin ligase (CRL) complex, targeting BRI2 and BRI3 (inhibitors of amyloid precursor protein processing) for degradation. Dimerized NRBP1 assembles a functional heterodimeric CRL through a BC-box and an overlapping cryptic H-box interacting with both Cul2 and Cul4A. Chaperone-like activity of TSC22D3 and TSC22D4 strongly enhances NRBP1 CRL formation. NRBP1 knockdown in neuronal cells increases BRI2/BRI3 abundance and reduces Aβ production. |
Mass spectrometry interactome, co-immunoprecipitation, ubiquitin ligase assay, siRNA knockdown, Aβ ELISA |
Cell reports |
High |
32160551
|
| 2021 |
NRBP1 is localized in microglia and neurons (not astrocytes) of mouse medial prefrontal cortex. (R)-ketamine increases NRBP1 expression in primary microglia through ERK activation, and NRBP1 operates in an ERK-NRBP1-CREB-BDNF signaling axis. (R)-ketamine activates BDNF transcription through CREB activation and MeCP2 suppression in microglia. |
iTRAQ proteomics, primary microglia culture, immunofluorescence localization, CREB/MeCP2 inhibition (HDO), CSF1R inhibitor microglial depletion, dendritic spine density assay |
Molecular psychiatry |
Medium |
34819637
|
| 2022 |
Drosophila Madm/NRBP1 is required presynaptically to maintain synaptic stability and coordinates synaptic growth and function by controlling cap-dependent translation via the TOR effector 4E-BP/Thor. Postsynaptic Madm induces a compensatory transsynaptic signal utilizing the presynaptic homeostatic potentiation (PHP) machinery via regulation of 4E-BP/Thor and S6-kinase, delaying synaptic degeneration. |
Cell-type-specific RNAi, genetic epistasis, electrophysiology (NMJ), 4E-BP phosphorylation assay, presynaptic homeostatic potentiation assay |
Cell reports |
High |
36450258
|
| 2023 |
NRBP1 pseudokinase binds P-Rex1 (a guanine nucleotide exchange factor for Rac1) as identified by BioID/MS profiling, and acts as a scaffold for a complex with P-Rex1, Rac1, and Cdc42. NRBP1 overexpression enhances GTP-bound Rac1 and Cdc42 levels in a P-Rex1-dependent manner, promoting TNBC cell migration, invasion, and proliferation via reactive oxygen species generation. |
BioID/MS proximity labeling, co-immunoprecipitation, GTP-Rac1/Cdc42 pull-down assay, siRNA knockdown, constitutively active Rac1 rescue, ROS assay, xenograft |
Oncogene |
High |
36693952
|
| 2024 |
TSC22D, WNK, and NRBP1 family members physically associate into biomolecular condensates within seconds of hyperosmotic stress, dependent on intrinsically disordered regions (IDRs). These protein families co-evolved in metazoans (TSC22D genes evolved alongside a domain in NRBPs, termed NbrT, that specifically binds TSC22D proteins) to co-regulate rapid cell volume changes in response to osmolarity. |
Gene co-essentiality analysis, live-cell imaging of condensate formation, co-immunoprecipitation, IDR deletion mutants, phylogenetic analysis |
Cell reports |
High |
38980795
|
| 2025 |
NRBP1 pseudokinase directly activates WNK4 kinase in vitro, and knockdown/knockout of NRBP1 markedly inhibits basal and sorbitol-induced activation of WNK1 and downstream SPAK/OSR1 components. NRBP1 contains a CCT-like domain that, together with TSC22D4 RΦ-motifs, is predicted (AlphaFold-3) to form a complex with WNK1 and SPAK. Osmotic stress promotes association of WNK1 with NRBP1 and TSC22D2/4 confirmed by immunoprecipitation and mass spectrometry. |
Proximity labeling, co-immunoprecipitation, mass spectrometry, immunoblotting, siRNA/CRISPR knockout, in vitro WNK4 kinase activation assay, AlphaFold-3 structural modeling |
Science advances |
High |
40668933
|
| 2025 |
DCT-specific NRBP1 knockout mice show reduced NCC phosphorylation and activate a compensatory response, demonstrating that NRBP1 and long TSC22D proteins are positive modulators of WNK signaling that regulate Na+ reabsorption in the distal convoluted tubule kidney. TSC22D1.1, TSC22D2, and NRBP1 co-localize in DCT WNK bodies (cytoplasmic biomolecular condensates associated with WNK activation). |
Tissue-specific knockout mouse, NCC phosphorylation assay, immunofluorescence co-localization, HEK293 cell WNK4 activity assay |
Science advances |
High |
40668923
|
| 2025 |
NRBP1 and its paralog NRBP2 oppositely regulate LINE1 (L1) retrotransposition by influencing integrity of the L1 ribonucleoprotein complex. NRBP2 targets NRBP1 for proteasome-mediated degradation, likely through heterodimer formation, accounting for their opposing roles rather than competition for shared binding partners. |
L1 retrotransposition reporter assay, co-immunoprecipitation, proteasome inhibitor rescue, heterodimer formation assay, phylogenetic analysis |
Nature communications |
High |
40645931
|
| 2025 |
TRIM24 E3 ubiquitin ligase binds NRBP1, enhances its ubiquitination and subsequent degradation. NRBP1 phosphorylation at residue S42 is required for TRIM24-mediated ubiquitination, and K430 is the specific ubiquitination site targeted by TRIM24. |
Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (S42, K430), siRNA knockdown, Western blotting |
Cell death & disease |
High |
41430038
|
| 2024 |
The NRBP1 CCT-like domain binds TSC22D1 via the same RΦ-motif as OSR1 and SPAK, including variants lacking the conserved arginine previously thought to be essential, revealing that NRBP1 participates in the WNK signaling network through CCT domain-mediated protein interactions. |
Motif interaction analysis, biochemical binding assays, CCT domain characterization |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.06.26.600905
|
| 2017 |
DNA methylation at the NRBP1 promoter region (72 bp upstream of TSS, site B1) increases binding of transcription factor TFAP2A, leading to suppressed NRBP1 expression. Hypomethylation reduces TFAP2A binding and elevates NRBP1 expression, as shown in gout patient PBMCs and in vitro. |
Luciferase reporter assay, protein pulldown assay, bisulfite pyrosequencing |
Clinical epigenetics |
Medium |
28932319
|