Publications by authors named "Vasiliki S Lalioti"

5 Publications

  • Page 1 of 1

Structural basis of Sorcin-mediated calcium-dependent signal transduction.

Sci Rep 2015 Nov 18;5:16828. Epub 2015 Nov 18.

Institute of Molecular Biology and Pathology CNR; Dept. Biochemical Sciences, Sapienza University, P.le A. Moro 5, 00185, Rome, Italy.

Sorcin is an essential penta-EF hand calcium binding protein, able to confer the multi-drug resistance phenotype to drug-sensitive cancer cells and to reduce Endoplasmic Reticulum stress and cell death. Sorcin silencing blocks cell cycle progression in mitosis and induces cell death by triggering apoptosis. Sorcin participates in the modulation of calcium homeostasis and in calcium-dependent cell signalling in normal and cancer cells. The molecular basis of Sorcin action is yet unknown. The X-ray structures of Sorcin in the apo (apoSor) and in calcium bound form (CaSor) reveal the structural basis of Sorcin action: calcium binding to the EF1-3 hands promotes a large conformational change, involving a movement of the long D-helix joining the EF1-EF2 sub-domain to EF3 and the opening of EF1. This movement promotes the exposure of a hydrophobic pocket, which can accommodate in CaSor the portion of its N-terminal domain displaying the consensus binding motif identified by phage display experiments. This domain inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin consensus motif, co-localizes with Sorcin in the perinuclear region of the cell and in the midbody and is involved in the onset of apoptosis.
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http://dx.doi.org/10.1038/srep16828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649501PMC
November 2015

Sorcin links calcium signaling to vesicle trafficking, regulates Polo-like kinase 1 and is necessary for mitosis.

PLoS One 2014 10;9(1):e85438. Epub 2014 Jan 10.

CNR-National Research Council of Italy, Institute of Molecular Biology and Pathology c/o Department of Biochemical Sciences "A. Rossi Fanelli", University "Sapienza" P.le A.Moro 5, Rome, Italy.

Sorcin, a protein overexpressed in many multi-drug resistant cancers, dynamically localizes to distinct subcellular sites in 3T3-L1 fibroblasts during cell-cycle progression. During interphase sorcin is in the nucleus, in the plasma membrane, in endoplasmic reticulum (ER) cisternae, and in ER-derived vesicles localized along the microtubules. These vesicles are positive to RyR, SERCA, calreticulin and Rab10. At the beginning of mitosis, sorcin-containing vesicles associate with the mitotic spindle, and during telophase are concentrated in the cleavage furrow and, subsequently, in the midbody. Sorcin regulates dimensions and calcium load of the ER vesicles by inhibiting RYR and activating SERCA. Analysis of sorcin interactome reveals calcium-dependent interactions with many proteins, including Polo-like kinase 1 (PLK1), Aurora A and Aurora B kinases. Sorcin interacts physically with PLK1, is phosphorylated by PLK1 and induces PLK1 autophosphorylation, thereby regulating kinase activity. Knockdown of sorcin results in major defects in mitosis and cytokinesis, increase in the number of rounded polynucleated cells, blockage of cell progression in G2/M, apoptosis and cell death. Sorcin regulates calcium homeostasis and is necessary for the activation of mitosis and cytokinesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085438PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888430PMC
October 2014

Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS.

Proc Natl Acad Sci U S A 2013 Jun 28;110(24):9794-9. Epub 2013 May 28.

Institute of Protein Biochemistry, National Research Council, 80131 Naples, Italy.

ADP-ribosylation is a posttranslational modification that modulates the functions of many target proteins. We previously showed that the fungal toxin brefeldin A (BFA) induces the ADP-ribosylation of C-terminal-binding protein-1 short-form/BFA-ADP-ribosylation substrate (CtBP1-S/BARS), a bifunctional protein with roles in the nucleus as a transcription factor and in the cytosol as a regulator of membrane fission during intracellular trafficking and mitotic partitioning of the Golgi complex. Here, we report that ADP-ribosylation of CtBP1-S/BARS by BFA occurs via a nonconventional mechanism that comprises two steps: (i) synthesis of a BFA-ADP-ribose conjugate by the ADP-ribosyl cyclase CD38 and (ii) covalent binding of the BFA-ADP-ribose conjugate into the CtBP1-S/BARS NAD(+)-binding pocket. This results in the locking of CtBP1-S/BARS in a dimeric conformation, which prevents its binding to interactors known to be involved in membrane fission and, hence, in the inhibition of the fission machinery involved in mitotic Golgi partitioning. As this inhibition may lead to arrest of the cell cycle in G2, these findings provide a strategy for the design of pharmacological blockers of cell cycle in tumor cells that express high levels of CD38.
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http://dx.doi.org/10.1073/pnas.1222413110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683763PMC
June 2013

C6orf89 encodes three distinct HDAC enhancers that function in the nucleolus, the golgi and the midbody.

J Cell Physiol 2013 Sep;228(9):1907-21

Centro de Biología Molecular Severo Ochoa, CSIC, Universidad Autónoma de Madrid, Departamento Biología Celular e Inmunología, Cantoblanco, Madrid, Spain.

We report here that C6orf89, which encodes a protein that interacts with bombesin receptor subtype-3 and accelerates cell cycle progression and wound repair in human bronchial epithelial cells (Liu et al., 2011, PLoS ONE 6: e23072), encodes one soluble and two type II membrane proteins that function as histone deacetylases (HDAC) enhancers. Soluble 34/64sp is selectively targeted to the nucleolus and is retained in nucleolar organiser regions (NORs) in mitotic cells. Nucleolar 34/64sp is integrated into the ribosomal gene transcription machinery, colocalises and coimmunoprecipitates with the Pol I transcription factor UBF, and undergoes a dramatic relocalisation to the nucleolus upon the arrest of rDNA transcription, protein synthesis and PI3K/mTORC2 signalling. Membrane 42/116mp localises to the Golgi and the midbody, and its controlled ectopic expression provokes the disruption of the Golgi cisternae and hinders the separation of daughter cells and the completion of mitosis. The latter effect is also produced by the microinjection of an affinity-purified amfion antibody. The identification of C60rf89 as a gene that encodes three distinct proteins with the capacity to enhance the activity of histone deacetylases (HDACs) in the nucleolus, the Golgi and the midbody provides new information regarding the components of the acetylome and their capacity to interact with different functional groups in the cell.
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http://dx.doi.org/10.1002/jcp.24355DOI Listing
September 2013

Daxx functions as a scaffold of a protein assembly constituted by GLUT4, JNK1 and KIF5B.

J Cell Physiol 2009 Feb;218(2):416-26

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid, Spain.

We have previously reported the physical interaction between Daxx, the adaptor protein that mediates activation of the Jun amino-terminal kinase (JNK), and GLUT4, the insulin-dependent glucose transporter, interaction that involves their C-domains. Co-immunoprecipitation and two-hybrid-based protein-protein interaction studies show now that Daxx and GLUT4 interact with JNK1 through D-sites in their NH(2)-(aa 1-501) and large endofacial loop, respectively. Serum deprivation strongly enhances the association of JNK1 with Daxx and dissociates the kinase from GLUT4. SP600125, a potent JNK1 inhibitor, reduces the JNK1 activity associated with GLUT4 and the phosphorylation of two minor GLUT4 species in serum-starved 3T3-L1 adipocytes. In addition, Daxx interacts with kinesin KIF5B through the 6xTPR domain of the kinesin light chain, a domain engaged in the grab hold of protein cargo by kinesin motors that codistribute with JNK. Depletion of Daxx in 3T3-L1 adipocytes provokes the partial translocation of the GLUT4 retained in the GLUT4 storage compartment to endosomes.
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http://dx.doi.org/10.1002/jcp.21614DOI Listing
February 2009