| 2010 |
RNF-121 (C. elegans ortholog) is an ER-membrane-anchored E3 ubiquitin ligase that targets beta-integrin PAT-3 for ERAD-dependent degradation; induction of RNF-121 reduced PAT-3::GFP levels while inhibition caused accumulation of PAT-3::GFP inclusions; genetic epistasis placed RNF-121 downstream of the UPR regulator PERK. |
C. elegans genetics, RNAi inactivation, GFP reporter assays, genetic epistasis with PERK and ERAD mutants, subcellular localization |
Molecular biology of the cell |
High |
20357004
|
| 2014 |
Human RNF121 localizes predominantly to the Golgi apparatus and positively regulates NF-κB activation downstream of TNF-α, TLR, NLR, RLR stimulation, and DNA damage; its RING domain catalytic activity is required; RNF121 knockdown impairs IκBα proteasomal degradation without altering RIP1 ubiquitination or IKK activation, and RNF121 co-immunoprecipitates with IκBα but does not directly ubiquitinate it. |
siRNA library screen (46 transmembrane E3 ligases), NF-κB luciferase reporter assay, RIP1 ubiquitination assay, IKK activation assay, IκBα degradation assay, Co-IP, RING domain mutant analysis |
Cell communication and signaling : CCS |
Medium |
25388546
|
| 2014 |
Human RNF121 localizes to the Golgi apparatus and its RING domain is required to suppress apoptosis; RNF121 knockdown inhibits cell growth and induces caspase-3-dependent apoptosis, and overexpression of wild-type but not RING-domain mutant RNF121 rescues this phenotype. |
siRNA knockdown, overexpression of WT vs. RING domain mutants, caspase-3 activation assay, PARP cleavage, pan-caspase inhibitor rescue (Z-VAD-FMK), subcellular localization |
Acta biochimica et biophysica Sinica |
Medium |
24928685
|
| 2015 |
RNF121 is present in the ER and cis-Golgi and facilitates two opposing fates of voltage-gated sodium channels (NaV): ubiquitin-mediated proteasomal degradation and, when co-expressed with auxiliary NaVβ subunits, membrane localization; loss-of-function mutations in zebrafish rnf121 cause the alligator motility mutant phenotype. |
Zebrafish forward genetics (alligator mutant), in vivo imaging, NaV channel degradation and localization assays, co-expression with NaVβ subunits, proteasome inhibitor experiments, subcellular fractionation/localization |
Proceedings of the National Academy of Sciences of the United States of America |
High |
25691753
|
| 2015 |
RNF121 is an ER-localized E3 ubiquitin ligase expressed in endothelial cells that recognizes newly synthesized VEGFR-2 in the ER, ubiquitinates it, and restricts its maturation and cell-surface expression; the RING finger domain is required for this activity; RNF121 overexpression reduces VEGFR-2 surface levels and inhibits VEGF-induced endothelial cell proliferation and angiogenesis, while RNF121 knockdown decreases VEGFR-2 ubiquitination and increases surface VEGFR-2. |
Co-IP, ubiquitination assay, shRNA knockdown, overexpression, VEGFR-2 maturation (glycosylation) assay, flow cytometry for surface expression, endothelial cell proliferation and angiogenesis assays, RING domain deletion mutant |
Traffic (Copenhagen, Denmark) |
High |
26602861
|
| 2019 |
RNF121 is required for transcription from AAV capsid-associated genomes but not from transfected plasmids; CRISPR KO of RNF121 causes transcriptional arrest of AAV genomes as shown by RNA Pol ChIP and mRNA half-life measurements; the catalytic RING domain of RNF121 is essential; blocking VCP/p97 completely restores AAV transgene expression in RNF121 KO cells, and DNAPK-Cs is upregulated in KO cells with DNA damage machinery enriched at stalled AAV transcription sites. |
CRISPR/Cas9 KO, RNA Pol II ChIP, mRNA half-life assay, proteasome/VCP inhibitor rescue, transcriptomic and proteomic analysis, RING domain mutant overexpression rescue |
PLoS pathogens |
High |
31386698
|
| 2022 |
RNF121 is required for K63-linked polyubiquitination of SARS-CoV-2 ORF7a; knockdown of RNF121 significantly decreased ORF7a binding to TAK1 and NEMO, resulting in suppression of NF-κB activation. |
RNF121 siRNA knockdown, ubiquitination assay (K63-linked), Co-IP of ORF7a with TAK1/NEMO, NF-κB luciferase reporter assay |
mBio |
Medium |
35856559
|
| 2022 |
Cryo-EM structure of the human GPI transamidase (GPIT) complex at 3.1 Å resolution reveals RNF121 associated at the back of the complex, interpreted as a quality control factor for the GPIT complex. |
Single-particle cryo-EM structural determination at 3.1 Å |
Nature structural & molecular biology |
Medium |
35165458
|
| 2024 |
RNF121 localizes to the cis-Golgi Complex via its transmembrane domain; a point mutation (M158R) in transmembrane helix 4 reduces RNF121 protein stability and abolishes Golgi localization; RNF121 directly binds MYCN protein and enhances its stability; transmembrane helix 5 is required for RNF121-enhanced growth of MYCN-amplified neuroblastoma cells; hemizygous RNF121 deletion reduces TH-MYCN-driven tumorigenicity in vivo. |
ENU mutagenesis screen, transgenic mouse tumor model, protein localization (immunofluorescence), Co-IP (RNF121–MYCN interaction), MYCN stability assay, domain mutant analysis (helix 5 deletion), hemizygous gene deletion in vivo |
Communications biology |
High |
39402275
|
| 2025 |
RNF121 acts as an E3 ubiquitin ligase that ubiquitinates CRTC1, targeting it for proteasomal degradation; HIPK2-mediated phosphorylation of CRTC1 at Ser36 prevents this RNF121-dependent ubiquitination, thereby stabilizing CRTC1 and maintaining the CRTC1-CBP-AR transcriptional complex that drives AMH expression. |
Co-immunoprecipitation, ubiquitination assay, HIPK2 inhibitor/knockdown experiments, phosphorylation-site mutagenesis (Ser36), in vitro and in vivo PCOS mouse model |
Biology direct |
Medium |
40537816
|
| 2012 |
C. elegans rnf-121 acts at least partially in parallel with rnf-5 and ccdc-55 to promote termination of distal tip cell migration; genetic interaction studies using RNAi and deletion alleles placed rnf-121 in a pathway targeting cell migration-related substrates including beta-integrin PAT-3. |
C. elegans genetic epistasis, RNAi depletion, deletion allele rnf-121(ok848), DTC migration phenotype scoring |
Mechanisms of development |
Medium |
22285439
|