Journal article Open Access

Small-molecule modulators of the ATPase VCP/p97 affect specific p97 cellular functions

Figuerola Conchas, Ainoa; Saarbach, Jacques; Daguer, Jean-Pierre; Cieren, Adeline; Barluenga, Sofia; Winssinger, Nicolas; Gotta, Monica


MARC21 XML Export

<?xml version='1.0' encoding='UTF-8'?>
<record xmlns="http://www.loc.gov/MARC21/slim">
  <leader>00000nam##2200000uu#4500</leader>
  <datafield tag="041" ind1=" " ind2=" ">
    <subfield code="a">eng</subfield>
  </datafield>
  <controlfield tag="005">20200120170600.0</controlfield>
  <controlfield tag="001">3539008</controlfield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland § Department of Organic Chemistry, University of Geneva, 1211 Geneva 4, Switzerland</subfield>
    <subfield code="0">(orcid)0000-0002-6959-587X</subfield>
    <subfield code="a">Saarbach, Jacques</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland § Department of Organic Chemistry, University of Geneva, 1211 Geneva 4, Switzerland</subfield>
    <subfield code="a">Daguer, Jean-Pierre</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">† Department of Cell Physiology and Metabolism, University of Geneva, 1211 Geneva 4, Switzerland ‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland</subfield>
    <subfield code="a">Cieren, Adeline</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland § Department of Organic Chemistry, University of Geneva, 1211 Geneva 4, Switzerland</subfield>
    <subfield code="a">Barluenga, Sofia</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland § Department of Organic Chemistry, University of Geneva, 1211 Geneva 4, Switzerland</subfield>
    <subfield code="0">(orcid)0000-0003-1636-7766</subfield>
    <subfield code="a">Winssinger, Nicolas</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="u">† Department of Cell Physiology and Metabolism, University of Geneva, 1211 Geneva 4, Switzerland ‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland</subfield>
    <subfield code="0">(orcid)0000-0002-4336-7860</subfield>
    <subfield code="a">Gotta, Monica</subfield>
  </datafield>
  <datafield tag="856" ind1="4" ind2=" ">
    <subfield code="s">1090340612</subfield>
    <subfield code="z">md5:7f543bdfad7586677f438df80faf4a3d</subfield>
    <subfield code="u">https://zenodo.org/record/3539008/files/p97 ACS ChemBio RAW Data.zip</subfield>
  </datafield>
  <datafield tag="542" ind1=" " ind2=" ">
    <subfield code="l">open</subfield>
  </datafield>
  <datafield tag="260" ind1=" " ind2=" ">
    <subfield code="c">2019-11-10</subfield>
  </datafield>
  <datafield tag="909" ind1="C" ind2="O">
    <subfield code="p">openaire</subfield>
    <subfield code="o">oai:zenodo.org:3539008</subfield>
  </datafield>
  <datafield tag="100" ind1=" " ind2=" ">
    <subfield code="u">† Department of Cell Physiology and Metabolism, University of Geneva, 1211 Geneva 4, Switzerland ‡ Swiss National Centre for Competence in Research in Chemical Biology, University of Geneva, Geneva, Switzerland</subfield>
    <subfield code="a">Figuerola Conchas, Ainoa</subfield>
  </datafield>
  <datafield tag="245" ind1=" " ind2=" ">
    <subfield code="a">Small-molecule modulators of the ATPase VCP/p97 affect specific p97 cellular functions</subfield>
  </datafield>
  <datafield tag="540" ind1=" " ind2=" ">
    <subfield code="u">https://creativecommons.org/licenses/by/4.0/legalcode</subfield>
    <subfield code="a">Creative Commons Attribution 4.0 International</subfield>
  </datafield>
  <datafield tag="650" ind1="1" ind2="7">
    <subfield code="a">cc-by</subfield>
    <subfield code="2">opendefinition.org</subfield>
  </datafield>
  <datafield tag="520" ind1=" " ind2=" ">
    <subfield code="a">&lt;p&gt;ABSTRACT: VCP/p97 belongs to the AAA+ ATPase family and has an essential role in several cellular processes ranging from cell division to protein homeostasis. Compounds targeting p97 inhibit the main ATPase domain and cause cell death. Here, using PNA-encoded chemical libraries, we have identified two small molecules that target the regulatory domain of p97, comprising the N-terminal and the D1 ATPase domains, and do not cause cell death. One molecule, &lt;strong&gt;NW1028&lt;/strong&gt;, inhibits the degradation of a p97-dependent reporter, whereas the other, &lt;strong&gt;NW1030&lt;/strong&gt;, increases it. ATPase assays show that &lt;strong&gt;NW1028&lt;/strong&gt; and &lt;strong&gt;NW1030&lt;/strong&gt; do not affect the main catalytic domain of p97. Mapping of the binding site using a photo-affinity conjugate points to a cleft at the interface of the N-terminal and the D1 ATPase domains. We have therefore discovered two new compounds that bind to the regulatory domain of p97 and modulate specific p97 cellular functions. Using these compounds, we have revealed a role for p97 in the regulation of mitotic spindle orientation in HeLa cells.&lt;/p&gt;</subfield>
  </datafield>
  <datafield tag="773" ind1=" " ind2=" ">
    <subfield code="n">doi</subfield>
    <subfield code="i">isVersionOf</subfield>
    <subfield code="a">10.5281/zenodo.3534380</subfield>
  </datafield>
  <datafield tag="024" ind1=" " ind2=" ">
    <subfield code="a">10.5281/zenodo.3539008</subfield>
    <subfield code="2">doi</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">publication</subfield>
    <subfield code="b">article</subfield>
  </datafield>
</record>
51
12
views
downloads
All versions This version
Views 5144
Downloads 1212
Data volume 13.1 GB13.1 GB
Unique views 4237
Unique downloads 66

Share

Cite as