1 Ocak 2023 Dergi makalesi Açık Erişim

Parlak, Gizem Cagla; Baris, Ibrahim; Gul, Seref; Kavakli, Ibrahim Halil

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/265946</identifier>
  <creators>
    <creator>
      <creatorName>Parlak, Gizem Cagla</creatorName>
      <givenName>Gizem Cagla</givenName>
      <familyName>Parlak</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Baris, Ibrahim</creatorName>
      <givenName>Ibrahim</givenName>
      <familyName>Baris</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Gul, Seref</creatorName>
      <givenName>Seref</givenName>
      <familyName>Gul</familyName>
      <affiliation>Bezmialem Vakif Univ, Inst Life Sci &amp; Biotechnol, Beykoz, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Kavakli, Ibrahim Halil</creatorName>
      <givenName>Ibrahim Halil</givenName>
      <familyName>Kavakli</familyName>
    </creator>
  </creators>
  <titles>
    <title>Functional Characterization Of The Cry2 Circadian Clock Component Variant P.Ser420Phe Revealed A New Degradation Pathway For Cry2</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2023</publicationYear>
  <dates>
    <date dateType="Issued">2023-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/265946</alternateIdentifier>
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  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.jbc.2023.105451</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Cryptochromes (CRYs) are essential components of the circadian clock, playing a pivotal role as transcriptional repressors. Despite their significance, the precise mechanisms underlying CRYs' involvement in the circadian clock remain incompletely understood. In this study, we identified a rare CRY2 variant, p.Ser420Phe, from the 1000 Genomes Project and Ensembl database that is located in the functionally important coiled-coil-like helix (CC-helix) region. Functional characterization of this variant at the cellular level revealed that p.Ser420Phe CRY2 had reduced repression activity on CLOCK:BMAL1-driven transcription due to its reduced affinity to the core clock protein PER2 and defective translocation into the nucleus. Intriguingly, the CRY2 variant exhibited an unexpected resistance to degradation via the canonical proteasomal pathway, primarily due to the loss of interactions with E3 ligases (FBXL3 and FBXL21), which suggests Ser-420 of CRY2 is required for the interaction with E3 ligases. Further studies revealed that wild-type and CRY2 variants are degraded by the lysosomal-mediated degradation pathway, a mechanism not previously associated with CRY2. Surprisingly, knockout mouse embryonic fibroblast cells indicated that the CRY2 variant caused a 7 h shorter circadian period length in contrast to the observed prolonged period length in CRY2-'- cell lines. In summary, this study reveals a hitherto unknown degradation pathway for CRY2, shedding new light on the regulation of circadian rhythm period length.&lt;/p&gt;</description>
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