A5005409216- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- Protist diversity and phylogeny
- Cancer Cells and Metastasis
- 14-3-3 protein interactions
- Cellular Mechanics and Interactions
- Chemical Reactions and Isotopes
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Cancer, Lipids, and Metabolism
- Cellular transport and secretion
- Protein Structure and Dynamics
- Micro and Nano Robotics
- Cancer Treatment and Pharmacology
- Protease and Inhibitor Mechanisms
- Bioinformatics and Genomic Networks
- Glycosylation and Glycoproteins Research
- Photoreceptor and optogenetics research
- DNA Repair Mechanisms
University of Minnesota
2013-2020
Microtubules are structural polymers inside of cells that subject to posttranslational modifications. These modifications create functionally distinct subsets microtubule networks in the cell, and acetylation is only modification takes place hollow lumen microtubule. Although it known α-tubulin acetyltransferase (αTAT1) primary enzyme responsible for acetylation, mechanism how αTAT1 enters access its sites not well understood. By performing biochemical assays, fluorescence electron...
ABSTRACT TPX2 is a widely conserved microtubule-associated protein that required for mitotic spindle formation and function. Previous studies have demonstrated the nucleation of microtubules around chromosomes; however, molecular mechanism by which promotes microtubule remains mystery. In this study, we found acts to suppress tubulin subunit off-rates during assembly disassembly, thus allowing support unprecedentedly slow rates plus-end growth, also leading dramatically reduced shortening...
The microtubule binding protein EB1 specifically targets the growing ends of microtubules in cells, where facilitates interactions cellular proteins with plus-ends. Microtubule end targeting has been attributed to high-affinity GTP-tubulin that is present at ends. However, our 3D single-molecule diffusion simulations predicted a ~ 6000% increase arrivals open, tapered tip structures relative closed lattice conformations. Using quantitative fluorescence, single-molecule, and electron...
Microtubules are structural polymers that participate in a wide range of cellular functions. The addition and loss tubulin subunits allows the microtubule to grow shorten, as well develop repair defects gaps its cylindrical lattice. These lattice act modulate interactions microtubules with molecular motors other microtubule-associated proteins. Therefore, tools control measure structure will be invaluable developing quantitative understanding for how state may regulate In this work, we...
UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family cochaperones, plays an important role in regulating cytoskeletal-associated functions invertebrates and mammalian cells, including cytokinesis, exocytosis, cell motility, neuronal development. Here, for first time, UNC-45A is demonstrated to function as mitotic spindle-associated that destabilizes microtubules (MT) activity. Using vitro biophysical reconstitution total internal reflection fluorescence microscopy...
In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only UNC-45A, all implicated regulating both Non-Muscle Myosin II (NMII)- microtubule (MT)-associated Here we show that both, vitro cells, UNC-45A binds to MT lattice leading bending, breakage depolymerization. Furthermore, destabilizes MTs independent its NMII C-terminal binding domain even presence inhibitor blebbistatin. These...
Abstract In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only UNC-45A, all implicated regulating both Non-Muscle Myosin II (NMII)- microtubule (MT)-associated Here we show for first time that: a) vitro UNC-45A binds to MT lattice weakens its integrity leading bending, breakage depolymerization, b) cells, overexpression causes loss mass increase breakages, c) destabilizes MTs...
Abstract The microtubule binding protein EB1 specifically targets the growing ends of microtubules in cells, where facilitates interactions cellular proteins with plus-ends. Microtubule end targeting has been attributed to high affinity GTP-tubulin that is present at ends. However, our 3D single-molecule diffusion simulations predicted a ∼6000% increase arrivals open, tapered tip structures relative closed lattice conformations. Using quantitative fluorescence, single-molecule, and electron...
<div>Abstract<p>UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family cochaperones, plays an important role in regulating cytoskeletal-associated functions invertebrates and mammalian cells, including cytokinesis, exocytosis, cell motility, neuronal development. Here, for first time, UNC-45A is demonstrated to function as mitotic spindle-associated that destabilizes microtubules (MT) activity. Using <i>in vitro</i> biophysical reconstitution...
<p>Loss of UNC-45A results in decrease proliferation rate</p>
<p>Linear range for quantitative Western blot analysis</p>
<p>UNC-45A overexpression results with decrease in MT stability</p>
<p>Supplementary Figure Legends</p>
<p>Effects on UNC-45A loss SKOV-3 ovarian cancer cells</p>
<p>Recombinant UNC-45A-GFP protein</p>
<p>Polyclonal and clones of paclitaxel-resistant ovarian cancer cells overcome cell death on multipolar spindles</p>
<p>Depletion of UNC-45A using a second shRNA-UNC-45A (#2) causes mitotic defects consistent with overly stable spindles</p>
<p>The UNC-45A antibody is specific in immunofluorescence</p>
<p>Supplementary Figure Legends</p>
<p>Specificity of the UNC-45A antibody in immunohistochemistry</p>