A5016286213- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- RNA Research and Splicing
- Cellular transport and secretion
- Plant Molecular Biology Research
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- Cellular Mechanics and Interactions
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- 14-3-3 protein interactions
- Prostate Cancer Treatment and Research
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Flowering Plant Growth and Cultivation
- Protein Tyrosine Phosphatases
University of Arizona
2016-2025
University of Arizona Cancer Center
2015-2025
University of North Carolina at Chapel Hill
2005-2009
Albert Einstein College of Medicine
2002-2007
Yeshiva University
2002-2005
University of California, Davis
1997-2003
EB1 is an evolutionarily conserved protein that localizes to the plus ends of growing microtubules. In yeast, homologue (BIM1) has been shown modulate microtubule dynamics and link microtubules cortex, but functions metazoan proteins remain unknown. Using a novel preparation Drosophila S2 cell line promotes attachment spreading, we visualized single in real time found depletion by RNA-mediated inhibition (RNAi) interphase cells causes dramatic increase nondynamic (neither nor shrinking),...
Restricting centriole duplication to once per cell cycle is critical for chromosome segregation and genomic stability, but the mechanisms underlying this block reduplication are unclear. Genetic analyses have suggested an involvement Skp/Cullin/F box (SCF)-class ubiquitin ligases in process. In study, we describe a mechanism prevent Drosophila melanogaster whereby SCF E3 ligase complex with F-box protein Slimb mediates proteolytic degradation of centrosomal regulatory kinase Plk4. We...
It is well established that multiple microtubule-based motors contribute to the formation and function of mitotic spindle, but how activities these interrelate remains unclear. Here we visualize spindle in living Drosophila embryos show pole movements are directed by a temporally coordinated balance forces generated three motors, cytoplasmic dynein, KLP61F, Ncd. Specifically, our findings suggest dynein acts move poles apart throughout mitosis this activity augmented KLP61F after...
Chromosomes move toward mitotic spindle poles by a Pacman-flux mechanism linked to microtubule depolymerization: chromosomes actively depolymerize attached plus ends (Pacman) while being reeled in the continual poleward flow of tubulin subunits driven minus-end depolymerization (flux). We report that Drosophila melanogaster incorporates activities three different severing enzymes, Spastin, Fidgetin, and Katanin. Spastin Fidgetin are utilized stimulate flux. Both proteins concentrate at...
Abstract Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for many cancers but not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to immunosuppressive tumor microenvironment (TME) and is associated with poor response ICIs. The primary source of inflammatory cytokine production inflammasome. Here, we identify PIM kinases as regulators inflammasome activation tumor-associated macrophages (TAMs). Analysis clinical data from a cohort naïve,...
Dynactin links cytoplasmic dynein and other motors to cargo is involved in organizing radial microtubule arrays. The largest subunit of dynactin, p150glued, binds the intermediate chain has an N-terminal microtubule-binding domain. To examine role binding by we replaced wild-type p150glued Drosophila melanogaster S2 cells with mutant ΔN-p150 lacking residues 1–200, which unable bind microtubules. Cells treated cytochalasin D were used for analysis movement along Strikingly, although both...
In animal cells, centrosomes nucleate microtubules that form polarized arrays to organize the cytoplasm. Drosophila presents an interesting paradox however, as centrosome-deficient mutant animals develop into viable adults. To understand this discrepancy, we analyzed behaviors of and in culture vivo, using a combination live-cell imaging, electron microscopy, RNAi. The canonical model cycle centrosome function cells states act microtubule-organizing centers throughout cell cycle....
Accurate and timely chromosome segregation is a task performed within meiotic mitotic cells by specialized force-generating structure – the spindle. This micromachine constructed from numerous proteins, most notably filamentous microtubules that form structural framework for spindle also transmit forces through it. Poleward flux an evolutionarily conserved mechanism used both to move chromosomes regulate length. Recent studies have identified microtubule-depolymerizing kinesin as key...
Centriole duplication is a tightly regulated process that must occur only once per cell cycle; otherwise, supernumerary centrioles can induce aneuploidy and tumorigenesis. Plk4 (Polo-like kinase 4) activity initiates centriole by ubiquitin-mediated proteolysis. Throughout interphase, autophosphorylation triggers its degradation, thus preventing amplification. However, required during mitosis for proper duplication, but the mechanism stabilizing mitotic unknown. In this paper, we show PP2A...
Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. II uniquely localizes to chromatin throughout the cell cycle and, addition its mitotic duties, modulates organization gene expression interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate interphase are unclear. Here, we report inactivated when subunit Cap-H2 targeted for degradation SCFSlimb ubiquitin ligase complex disruption of this process...
Significance Polo-like kinases (Plks) are a conserved family of enzymes that function as master regulators for the process cell division. Among their duties, Plks control assembly centrosomes, tiny organelles facilitate mitotic spindle and maintain fidelity chromosome inheritance. overexpressed in cancer, therefore it is critical to unravel normal regulation these kinases. Here, we studied Plk4 whose activity controls centrosome number. We showed that, do other Plks, autoinhibits its kinase...
Abstract The centrosome is the major microtubule-organizing centre of many cells, best known for its role in mitotic spindle organization. How proteins are accurately assembled to carry out functions remains poorly understood. non-membrane-bound nature dictates that protein–protein interactions drive assembly and functions. To investigate this massive macromolecular organelle, we generated a ‘domain-level’ interactome using direct interaction data from focused yeast two-hybrid screen. We...
Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to central coiled-coil (CC) Ana2 is conserved event involving Polo-box 3 and previously unidentified putative CC located adjacent domain. then phosphorylated along its length. Previous studies showed phosphorylates C-terminal STil/ANa2 (STAN) domain triggering recruitment cartwheel protein Sas6 procentriole site....
Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making detailed understanding of its regulation extremely important. Germaine to pericentrin's function PCM ability localize centrosome through conserved C-terminal PACT domain. Here we use Drosophila pericentrin-like-protein (PLP) understand how domain...