Topic
HAUS complex
About: HAUS complex is a research topic. Over the lifetime, 4 publications have been published within this topic receiving 80 citations.
Papers
TL;DR: It is reported that ZNF131 is broadly required for Glioblastoma stem-like cell viability, but dispensable for neural progenitor cell (NPC) viability, and suggested that GSCs differentially rely on ZNF 131-dependent expression of HAUS5 as well as the Augmin/HAUS complex activity to maintain the integrity of centrosome function and viability.
Abstract: // Yu Ding 1,6 , Jacob A. Herman 1,2 , Chad M. Toledo 1,3,7 , Jackie M. Lang 2,3 , Philip Corrin 1 , Emily J. Girard 4 , Ryan Basom 5 , Jeffrey J. Delrow 5 , James M. Olson 4 and Patrick J. Paddison 1,3 1 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 2 Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 3 Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA 4 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 5 Genomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 6 Novartis Institute for Biomedical Research, Shanghai, China 7 Nurix Inc., San Francisco, CA, USA Correspondence to: Patrick J. Paddison, email: // Keywords : glioblastoma, ZNF131, HAUS5, Augmin/HAUS complex, cancer therapeutics Received : February 17, 2017 Accepted : May 05, 2017 Published : May 24, 2017 Abstract Zinc finger domain genes comprise ~3% of the human genome, yet many of their functions remain unknown. Here we investigated roles for the vertebrate-specific BTB domain zinc finger gene ZNF131 in the context of human brain tumors. We report that ZNF131 is broadly required for Glioblastoma stem-like cell (GSC) viability, but dispensable for neural progenitor cell (NPC) viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7 , NPHP1 , and TMEM237 , as well as HAUS5 , a component of Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle. Of these genes only kd of HAUS5 displayed GSC-specific viability loss. Critically, HAUS5 ectopic expression was sufficient to suppress viability defects of ZNF131 kd cells. Moreover, ZNF131 and HAUS5 kd phenocopied each other in GSCs, each causing: mitotic arrest, centrosome fragmentation, loss of Augmin/HAUS complex on the mitotic spindle, and loss of GSC self-renewal and tumor formation capacity. In control NPCs, we observed centrosome fragmentation and lethality only when HAUS5 kd was combined with kd of HAUS 2 or HAUS4 , demonstrating that the complex is essential in NPCs, but that GSCs have heightened requirement. Our results suggest that GSCs differentially rely on ZNF131 -dependent expression of HAUS5 as well as the Augmin/HAUS complex activity to maintain the integrity of centrosome function and viability.
24 citations
TL;DR: The results suggest that UCHL5IP plays critical roles in spindle formation during mouse oocyte meiotic maturation and it was localised to the meiotic spindle in MI and MII stages.
Abstract: UCHL5IP is one of the subunits of the haus complex, which is important for microtubule generation, spindle bipolarity and accurate chromosome segregation in Drosophila and human mitotic cells. In this study, the expression and localisation of UCHL5IP were explored, as well as its functions in mouse oocyte meiotic maturation. The results showed that the UCHL5IP protein level was consistent during oocyte maturation and it was localised to the meiotic spindle in MI and MII stages. Knockdown of UCHL5IP led to spindle defects, chromosome misalignment and disruption of γ-tubulin localisation in the spindle poles. These results suggest that UCHL5IP plays critical roles in spindle formation during mouse oocyte meiotic maturation.
3 citations
TL;DR: It is proposed that the HAUS complex locally regulates microtubule nucleation events to control proper neuronal development and migration, development, and polarization.
TL;DR: A wealth of information has recently become available driven by new developments in technologies such as mass spectrometry, light and electron microscopy providing more detailed molecular and structural definition of the centrosome and particular roles of proteins throughout the cell cycle and development.
Abstract: This review provides a brief overview of the recent work on centrosome proteomics, protein complex identification and functional characterization with an emphasis on the literature of the last three years. Proteomics, genetic screens and comparative genomics studies in different model organisms have almost exhaustively identified the molecular components of the centrosome. However, much knowledge is still missing on the protein-protein interactions, protein modifications and molecular changes the centrosome undergoes throughout the cell cycle and development. The dynamic nature of this large multi-protein complex is reflected in the variety of annotated subcellular locations and biological processes of its proposed components. Some centrosomal proteins and complexes have been studied intensively in different organisms and provided detailed insight into centrosome functions. For example, the molecular, structural and functional characterization of the γ-Tubulin ring complex (γ-TuRC) and the the discovery of the Augmin/HAUS complex has advanced our understanding of microtubule (MT) capture, nucleation and organization. Surprising findings revealed new functions and localizations of proteins that were previously regarded as bona fide centriolar or centrosome components, e.g. at the kinetochore or in the nuclear pore complex regulating MT plus end capture or mRNA processing. Many centrosome components undergo posttranslational modifications such as phosphorylation, SUMOylation and ubiquitylation that are critical in modulating centrosome function and biology. A wealth of information has recently become available driven by new developments in technologies such as mass spectrometry, light and electron microscopy providing more detailed molecular and structural definition of the centrosome and particular roles of proteins throughout the cell cycle and development.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2018 | 1 |
| 2017 | 1 |
| 2012 | 2 |