| 2010 |
NudCL2 (NUDCD2) localizes to centrosomes in interphase and to spindle poles and kinetochores during mitosis. Depletion of NudCL2 destabilizes LIS1 protein and produces phenotypes resembling dynein or LIS1 deficiency. NudCL2 forms a complex with LIS1 and Hsp90, enhancing the LIS1–Hsp90 interaction; disruption of this interaction (via NudCL2 C-terminus overexpression) or inhibition of Hsp90 (geldanamycin) reduces LIS1 stability. Thus NudCL2 stabilizes LIS1 through the Hsp90 chaperone pathway. |
Immunofluorescence localization, co-immunoprecipitation, RNAi knockdown, western blotting, geldanamycin Hsp90 inhibition, C-terminus dominant-negative construct |
Proceedings of the National Academy of Sciences of the United States of America |
High |
20133715
|
| 2011 |
Crystal and NMR structures of NudCL2 (mouse) show it shares a CS/p23 domain with other NudC family members but lacks the N-terminal coiled-coil dimerization motif; instead it dimerizes via unique domain swapping. In contrast to NudC and NudCL, NudCL2 does NOT inhibit aggregation of target proteins in vitro, indicating it lacks Hsp90-independent small heat-shock-protein chaperone activity. Additionally, none of the three NudC proteins form binary complexes with Lis1 in vitro. |
X-ray crystallography, NMR spectroscopy, in vitro aggregation chaperone assays, pull-down/binding assays |
Journal of molecular biology |
High |
21530541
|
| 2018 |
NudCL2 acts as an Hsp90 cochaperone that stabilizes cohesin subunits (SMC1, SMC3, RAD21, SA1/SA2) in mammalian cells. NudCL2 directly binds Hsp90 and stimulates its ATPase activity, enhancing Hsp90 chaperone function. Depletion of NudCL2 causes premature sister chromatid separation and mitotic defects; ectopic Hsp90 overexpression rescues cohesin instability caused by NudCL2 loss, but NudCL2 overexpression does not rescue Hsp90-inhibition phenotypes, placing NudCL2 upstream of Hsp90 in this pathway. |
Co-immunoprecipitation, western blotting, RNAi knockdown, Hsp90 ATPase activity assay, epistasis by rescue experiments (Hsp90 overexpression vs NudCL2 overexpression), mitotic chromosome spread analysis |
Cellular and molecular life sciences : CMLS |
High |
30368549
|
| 2019 |
NudCL2 localizes to centrosomes and is required for accurate centriole duplication. Knockout or knockdown of NudCL2 causes centriole amplification; overexpression suppresses hydroxyurea-induced over-duplication. NudCL2 interacts with and stabilizes the E3 ubiquitin ligase HERC2. Loss of HERC2 phenocopies NudCL2 depletion and leads to accumulation of the positive centriole-duplication regulator USP33; knockdown of USP33 reverses centriole amplification in both NudCL2 KO and HERC2-depleted cells. Ectopic HERC2 rescues NudCL2-KO centriole amplification; NudCL2 overexpression does not rescue HERC2-depletion phenotype, defining the NudCL2→HERC2→USP33 pathway. |
CRISPR/Cas9 KO, RNAi, quantitative proteomics (iTRAQ), co-immunoprecipitation, western blotting, epistasis rescue experiments, immunofluorescence |
Cell death & disease |
High |
31427565
|
| 2020 |
NudCL2 regulates single-cell (but not collective) migration by stabilizing both myosin-9 (MYH9) and LIS1 via Hsp90. NudCL2 binds myosin-9 (identified by Co-IP-mass spectrometry). NudCL2 depletion reduces myosin-9 levels and causes actin disorganization; ectopic myosin-9 rescues actin and single-cell migration defects. LIS1 depletion suppresses both single and collective migration (opposite to myosin-9 depletion); co-depletion of myosin-9 and LIS1 phenocopies NudCL2 depletion. Hsp90 inhibition also reduces myosin-9 stability; Hsp90 overexpression rescues myosin-9 instability caused by NudCL2 depletion. |
Co-immunoprecipitation coupled to mass spectrometry, RNAi knockdown, CRISPR KO, western blotting, actin staining, migration assays (single-cell and scratch wound), rescue overexpression experiments |
Cell death & disease |
High |
32665550
|
| 2021 |
NudCL2 functions as a selective autophagy receptor at mother centrioles, containing an LIR (LC3-interacting region) motif that bridges CP110 to the autophagosome marker LC3, thereby promoting autophagic degradation of CP110 and enabling ciliogenesis initiation. NudCL2 KO prevents CP110 removal from mother centrioles and blocks ciliogenesis; wild-type but not LIR-mutant NudCL2 rescues these defects. CP110 knockdown attenuates ciliogenesis defects in NudCL2-deficient cells. In zebrafish, NudCL2 morphants show ciliation-related phenotypes reversed by wild-type but not LIR-mutant NudCL2, and by CP110 depletion. |
CRISPR/Cas9 KO, RNAi, co-immunoprecipitation (NudCL2–LC3, NudCL2–CP110), LIR-motif mutagenesis, immunofluorescence, zebrafish morpholino knockdown, rescue experiments |
Cell research |
High |
34480124
|
| 2024 |
NudCL2 localizes to the midbody and is required for cytokinesis. Its depletion causes cytokinesis failure, multinucleation, and midbody disorganization. iTRAQ quantitative proteomics identified RCC2 as downregulated in NudCL2 KO cells. NudCL2 interacts with RCC2, and Hsp90 forms a complex with NudCL2 to stabilize RCC2. RCC2 depletion phenocopies NudCL2 loss; ectopic RCC2 rescues NudCL2-KO cytokinesis defects, but NudCL2 overexpression does not rescue RCC2-depletion defects, establishing a NudCL2/Hsp90/RCC2 pathway for cytokinesis. |
CRISPR/Cas9 KO, RNAi, iTRAQ quantitative proteomics, co-immunoprecipitation, western blotting, immunofluorescence (midbody localization), epistasis rescue experiments |
Protein & cell |
High |
38801297
|
| 2024 |
RetSat interacts with cohesin/condensin components SMC1A and NudCL2 (NUDCD2) in embryonic stem cells; RetSat deletion impairs chromosome loading of SMC1A, SMC3, and NudCL2, linking NudCL2 to chromosome condensation/cohesion in pluripotent cells. |
Co-immunoprecipitation, LC-MS/MS, immunoblotting, immunostaining, RetSat KO mouse ESCs |
Cellular and molecular life sciences : CMLS |
Medium |
39172275
|
| 2025 |
NudCL2 suppresses pancreatic cancer cell invasion and metastasis by regulating the transcriptional activity of SLC7A11; NudCL2 depletion upregulates SLC7A11, activating the EMT pathway. SLC7A11 knockdown reverses the increased motility caused by NudCL2 loss, placing SLC7A11 downstream of NudCL2 in EMT regulation. |
RNAi knockdown, invasion/migration assays, in vivo lung and liver metastasis models, western blotting, transcriptional activity assay, epistasis (SLC7A11 KD reversal of NudCL2-KD phenotype) |
Experimental cell research |
Medium |
40907782
|