1 Ocak 2023 Dergi makalesi Açık Erişim

Wong, Samantha; Tan, Yu Xuan; Loh, Abigail Yi Ting; Tan, Kiat Yi; Lee, Hane; Aziz, Zainab; Nelson, Stanley F.; Ozkan, Engin; Kayserili, Hülya; Escande-Beillard, Nathalie; Reversade, Bruno

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/270832</identifier>
  <creators>
    <creator>
      <creatorName>Wong, Samantha</creatorName>
      <givenName>Samantha</givenName>
      <familyName>Wong</familyName>
    </creator>
    <creator>
      <creatorName>Tan, Yu Xuan</creatorName>
      <givenName>Yu Xuan</givenName>
      <familyName>Tan</familyName>
      <affiliation>ASTAR, Inst Mol &amp; Cellular Biol, Singapore, Singapore</affiliation>
    </creator>
    <creator>
      <creatorName>Loh, Abigail Yi Ting</creatorName>
      <givenName>Abigail Yi Ting</givenName>
      <familyName>Loh</familyName>
    </creator>
    <creator>
      <creatorName>Tan, Kiat Yi</creatorName>
      <givenName>Kiat Yi</givenName>
      <familyName>Tan</familyName>
      <affiliation>ASTAR, Inst Mol &amp; Cellular Biol, Singapore, Singapore</affiliation>
    </creator>
    <creator>
      <creatorName>Lee, Hane</creatorName>
      <givenName>Hane</givenName>
      <familyName>Lee</familyName>
    </creator>
    <creator>
      <creatorName>Aziz, Zainab</creatorName>
      <givenName>Zainab</givenName>
      <familyName>Aziz</familyName>
      <affiliation>Univ Chicago, Dept Biochem &amp; Mol Biol, Chicago, IL USA</affiliation>
    </creator>
    <creator>
      <creatorName>Nelson, Stanley F.</creatorName>
      <givenName>Stanley F.</givenName>
      <familyName>Nelson</familyName>
    </creator>
    <creator>
      <creatorName>Ozkan, Engin</creatorName>
      <givenName>Engin</givenName>
      <familyName>Ozkan</familyName>
      <affiliation>Univ Chicago, Dept Biochem &amp; Mol Biol, Chicago, IL USA</affiliation>
    </creator>
    <creator>
      <creatorName>Kayserili, Hülya</creatorName>
      <givenName>Hülya</givenName>
      <familyName>Kayserili</familyName>
      <affiliation>Koc Univ, Sch Med, Dept Med Genet, Istanbul, Turkiye</affiliation>
    </creator>
    <creator>
      <creatorName>Escande-Beillard, Nathalie</creatorName>
      <givenName>Nathalie</givenName>
      <familyName>Escande-Beillard</familyName>
    </creator>
    <creator>
      <creatorName>Reversade, Bruno</creatorName>
      <givenName>Bruno</givenName>
      <familyName>Reversade</familyName>
    </creator>
  </creators>
  <titles>
    <title>Raf1 Deficiency Causes A Lethal Syndrome That Underscores Rtk Signaling During Embryogenesis</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/270832</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.15252/emmm.202217078</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;Somatic and germline gain-of-function point mutations in RAF, one of the first oncogenes to be discovered in humans, delineate a group of tumor-prone syndromes known as the RASopathies. In this study, we document the first human phenotype resulting from the germline loss-of-function of the proto-oncogene RAF1 (a.k.a. CRAF). In a consanguineous family, we uncovered a homozygous p.Thr543Met variant segregating with a neonatal lethal syndrome with cutaneous, craniofacial, cardiac, and limb anomalies. Structure-based prediction and functional tests using human knock-in cells showed that threonine 543 is essential to: (i) ensure RAF1's stability and phosphorylation, (ii) maintain its kinase activity toward substrates of the MAPK pathway, and (iii) protect from stress-induced apoptosis mediated by ASK1. In Xenopus embryos, mutant RAF1(T543M) failed to phenocopy the effects of normal and overactive FGF/MAPK signaling, confirming its hypomorphic activity. Collectively, our data disclose the genetic and molecular etiology of a novel lethal syndrome with progeroid features, highlighting the importance of RTK signaling for human development and homeostasis.&lt;/p&gt;</description>
  </descriptions>
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