| 2018 |
Upon mTORC1 inhibition or nutrient starvation, NUFIP1 redistributes from the nucleus to autophagosomes and lysosomes, where it directly binds LC3B to deliver ribosomes to autophagosomes, functioning as a selective autophagy receptor (ribophagy receptor). This starvation-induced ribophagy depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival. |
Quantitative lysosome proteomics, co-immunoprecipitation (NUFIP1-LC3B interaction), subcellular fractionation/imaging, loss-of-function (NUFIP1 knockdown with cell survival readout), mTORC1 inhibition experiments |
Science |
High |
29700228
|
| 2003 |
NUFIP1 is a nucleocytoplasmic shuttling protein: it localizes in the nuclear matrix in RNA-containing structures, is also present in the cytoplasm associated with ribosomes, and is detected in functional synaptoneurosomes in neurons where it co-localizes with ribosomes. NUFIP1 contains a functional CRM1-dependent nuclear export signal mediating its shuttling between nucleus and cytoplasm. |
Subcellular fractionation, immunofluorescence imaging, synaptosome isolation and immunodetection, leptomycin B (CRM1 inhibitor) treatment demonstrating nuclear export signal function |
Experimental cell research |
Medium |
12941608
|
| 2013 |
NUFIP1 (the human homolog of yeast Rsa1p) acts as a scaffold/assembly factor for box C/D snoRNPs by directly interacting with the RNA-binding core protein 15.5K (human homolog of yeast Snu13p). NMR structure determination and docking identified the interface: residues R249, R246, K250 of Rsa1p and E72, D73 of Snu13p form electrostatic interactions, with W253 of Rsa1p inserted in a hydrophobic cavity of Snu13p. This interaction is predicted to be exclusive of interactions in active snoRNPs, suggesting Rsa1p/NUFIP1 prevents premature snoRNP activity. |
NMR structure determination, biophysical interaction assays, site-directed mutagenesis in yeast (cell growth and snoRNP formation readouts), molecular docking |
Nucleic acids research |
High |
24234454
|
| 2014 |
NUFIP1 (human functional homolog of yeast Rsa1p) interacts with ZNHIT3 (TRIP3, human homolog of yeast Hit1p), which stabilizes NUFIP1 protein levels. The yeast Rsa1p-Hit1p complex structure was determined by NMR, revealing a novel mode of protein-protein association. The purified Snu13p-Rsa1p-Hit1p heterotrimer can interact with C/D snoRNAs and core protein Nop58, placing NUFIP1 within the snoRNP assembly pathway. |
Proteomic (pulldown/MS), NMR structure determination of yeast Rsa1p-Hit1p complex, functional studies (C/D snoRNA stability, pre-RNA maturation), in vitro binding with purified heterotrimer, demonstration that human ZNHIT3 regulates NUFIP1 abundance |
Nucleic acids research |
High |
25170085
|
| 2004 |
NUFIP (NUFIP1) interacts with BRCA1 (identified by yeast two-hybrid) and with the P-TEFb complex via its Cyclin T1 subunit. NUFIP stimulates activator-independent RNA polymerase II transcription in vitro and in vivo; immunodepletion of endogenous NUFIP markedly decreases pol II transcription. NUFIP associates with preinitiation, open, and elongation complexes, and facilitates ATP-dependent dissociation of hyperphosphorylated pol II from open transcription complexes in vitro. Mutation of the zinc-finger domain abolishes NUFIP-mediated transcriptional activation. |
Yeast two-hybrid, immunodepletion + in vitro transcription assay, co-immunoprecipitation, in vitro transcription reconstitution, zinc-finger domain mutagenesis, in vivo reporter assay in 293 cells |
Oncogene |
Medium |
15107825
|
| 2019 |
Under cyclic mechanical stress (CMS) in trabecular meshwork cells, nuclear LC3 co-immunoprecipitates with NUFIP1 in the nucleolus. NUFIP1 translocates from the nucleus to LAMP2-positive (lysosomal) organelles in mechanically stretched cells, but without triggering ribophagy, suggesting a more general role of NUFIP1 as a selective autophagy receptor for a target other than ribosomes under mechanical stress. |
Co-immunoprecipitation, biochemical fractionation, immunofluorescence imaging, adenoviral GFP-LC3 expression, leptomycin B treatment |
Autophagy |
Medium |
31476975
|
| 2025 |
Under amino acid deficiency, phosphorylated NUFIP1 binds replication protein A2 (RPA32) to recruit the ATR-ATRIP complex, triggering the DNA damage response (DDR). Loss of NUFIP1 impairs the DDR and induces necroptosis-related spontaneous enteritis in vivo; reintroduction of NUFIP1 but not its non-phosphorylatable mutant rescues bowel inflammation in conditional knockout mice. |
Co-immunoprecipitation (phospho-NUFIP1 with RPA32/ATR-ATRIP), conditional knockout mouse model, non-phospho-mutant rescue experiments, in vitro cell DDR assays |
Nature metabolism |
Medium |
39753713
|
| 2025 |
In sepsis, ribosome collision activates the cGAS-STING signaling axis, which recruits NUFIP1 to STING protein complexes. NUFIP1-mediated ribophagy suppresses ZBP1-mediated PANoptosome formation and PANoptosis in CD4+ T lymphocytes; NUFIP1 knockdown exacerbates PANoptosis and impairs T cell function (cytokine production, proliferation). |
Tandem mass tagging (TMT) proteomics, Co-IP (NUFIP1-STING interaction), NUFIP1 knockdown in Jurkat T cells, cecal ligation and puncture sepsis mouse model, clinical CD4+ T cell analysis |
Research (Washington, D.C.) |
Medium |
40995563
|
| 2022 |
In cancer-associated fibroblasts (CAFs), NUFIP1-dependent autophagy (ribophagy) mediates secretion of nucleosides that support pancreatic tumor growth and glucose utilization under glutamine deprivation. Inhibiting nucleoside secretion by targeting NUFIP1 in stromal cells reduced tumor weight in an orthotopic mouse model. |
NUFIP1 knockdown/inhibition in CAFs, orthotopic PDAC mouse model, metabolite (nucleoside) measurement, MYC-dependence analysis |
Nature cancer |
Medium |
35982178
|