Ask about this productRelated genes to: NDE1 antibody
- Gene:
- NDE1 NIH gene
- Name:
- nudE neurodevelopment protein 1
- Previous symbol:
- -
- Synonyms:
- nudE, FLJ20101, NDE
- Chromosome:
- 16p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-10
- Date modifiied:
- 2014-11-18
- Gene:
- NDEL1 NIH gene
- Name:
- nudE neurodevelopment protein 1 like 1
- Previous symbol:
- -
- Synonyms:
- NUDEL, MITAP1, NDE1L1, NDE2
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-10
- Date modifiied:
- 2016-01-06
Related products to: NDE1 antibody
Related articles to: NDE1 antibody
- Recent studies have identified recurrent features of metastatic cancer cells such as their increased chromosomal instability (CIN) and frequent loss of the short arm of chromosome 17 (Chr17p). However, it remains unclear whether these features induce synthetic lethal vulnerabilities that can be used to specifically target metastatic disease. Using whole-genome CRISPR/Cas9 loss-of-function screens performed in matched primary and CIN-high brain-metastatic tumor models, we discovered that brain-metastatic cells exhibit increased sensitivity to the loss of diverse regulators of chromosome segregation. Knockout of one such regulator, selectively inhibited the growth of brain-metastatic models and , an effect driven by the loss of STAG2 and consequent induction of CIN. Surprisingly, dependence on was also highly correlated with loss of Chr17p across hundreds of cancer cell lines in DepMap, the result of losing the paralog , which resides at this locus. CIN and Chr17p loss are thus independently sufficient to drive dependence in brain-metastatic cells, and the presence of both features increases dependence additively. These findings demonstrate that metastasis evolution endows cancer cells with specific vulnerabilities, including one that is driven by two recurrently altered molecular features of metastatic disease. - Source: PubMed
Publication date: 2026/02/12
Teddy Caroline MHoj Jacob PCaci JuliaLu MinKillarney Shane TBen-Yishay TalBen-David UriWood Kris C - Cytoplasmic dynein 1 (dynein) is the primary motor responsible for the retrograde transport of intracellular cargoes along microtubules. Activation of dynein requires the opening its autoinhibited Phi conformation, a process driven by Lis1 and Nde1/Ndel1. Using biochemical reconstitution and cryo-electron microscopy, we demonstrate that Nde1 enhances Lis1 binding to autoinhibited dynein and facilitates Phi opening. We identify a key intermediate in this activation pathway where a single Lis1 dimer binds between Phi-like (Phi) motor rings. In this 'Phi-Lis1' complex, Lis1 interacts with one motor domain through canonical sites at the AAA+ (adenosine triphosphatases associated with diverse cellular activities) ring and stalk, and with AAA5, AAA6 and linker regions of the other motor domain. Mutagenesis and motility assays confirm the critical role of the Phi-Lis1 interface in dynein activation. This intermediate forms rapidly in the presence of Nde1, although Nde1 is not part of Phi-Lis1. These findings provide key insights into how Nde1 promotes Lis1-mediated Phi opening. - Source: PubMed
Publication date: 2025/08/01
Yang JunZhao YuanchangChai PengxinYildiz AhmetZhang Kai - Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi. We discover a key intermediate step in the dynein activation pathway where a single Lis1 dimer binds between the Phi-like (Phi) motor rings of dynein. In this "Phi-Lis1", Lis1 interacts with one of the motor domains through its canonical interaction sites at the AAA+ ring and stalk and binds to the newly identified AAA5, AAA6, and linker regions of the other motor domain. Mutagenesis and motility assays confirm the critical role of the Phi-Lis1 interface. This intermediate state is instantly and efficiently formed in the presence of Nde1, but Nde1 is not part of the Phi-Lis1. These findings provide key insights into the mechanism of how Nde1 promotes the Lis1-mediated opening of Phi dynein. - Source: PubMed
Publication date: 2025/01/22
Yang JunZhao YuanchangChai PengxinYildiz AhmetZhang Kai - The development of the cerebral cortex involves a series of dynamic events, including cell proliferation and migration, which rely on the motor protein dynein and its regulators NDE1 and NDEL1. While the loss of function in NDE1 leads to microcephaly-related malformations of cortical development (MCDs), NDEL1 variants have not been detected in MCD patients. Here, we identified two patients with pachygyria, with or without subcortical band heterotopia (SBH), carrying the same de novo somatic mosaic NDEL1 variant, p.Arg105Pro (p.R105P). Through single-cell RNA sequencing and spatial transcriptomic analysis, we observed complementary expression of Nde1/NDE1 and Ndel1/NDEL1 in neural progenitors and post-mitotic neurons, respectively. Ndel1 knockdown by in utero electroporation resulted in impaired neuronal migration, a phenotype that could not be rescued by p.R105P. Remarkably, p.R105P expression alone strongly disrupted neuronal migration, increased the length of the leading process, and impaired nucleus-centrosome coupling, suggesting a failure in nucleokinesis. Mechanistically, p.R105P disrupted NDEL1 binding to the dynein regulator LIS1. This study identifies the first lissencephaly-associated NDEL1 variant and sheds light on the distinct roles of NDE1 and NDEL1 in nucleokinesis and MCD pathogenesis. - Source: PubMed
Publication date: 2024/01/09
Tsai Meng-HanKe Hao-ChenLin Wan-CianNian Fang-ShinHuang Chia-WeiCheng Haw-YuanHsu Chi-SinGranata TizianaChang Chien-HuiCastellotti BarbaraLin Shin-YiDoniselli Fabio MLu Cheng-JuFranceschetti SilvanaRagona FrancescaHou Pei-ShanCanafoglia LauraTung Chien-YiLee Mei-HsuanWang Won-JingTsai Jin-Wu - Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhibited conformation, but the physiological function of Nde1/Ndel1 remains elusive. Here, we investigate how human Nde1 and Lis1 regulate the assembly and subsequent motility of mammalian dynein using in vitro reconstitution and single molecule imaging. We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. Nde1 can compete with the α2 subunit of platelet activator factor acetylhydrolase 1B (PAF-AH1B) for the binding of Lis1, which suggests that Nde1 may disrupt PAF-AH1B recruitment of Lis1 as a noncatalytic subunit, thus promoting Lis1 binding to dynein. Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. Our results provide a mechanistic explanation for how Nde1 and Lis1 synergistically activate the dynein transport machinery. - Source: PubMed
Publication date: 2023/11/09
Zhao YuanchangOten SenaYildiz Ahmet