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

Dublin Core

<?xml version='1.0' encoding='utf-8'?>
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Wong, Samantha</dc:creator>
  <dc:creator>Tan, Yu Xuan</dc:creator>
  <dc:creator>Loh, Abigail Yi Ting</dc:creator>
  <dc:creator>Tan, Kiat Yi</dc:creator>
  <dc:creator>Lee, Hane</dc:creator>
  <dc:creator>Aziz, Zainab</dc:creator>
  <dc:creator>Nelson, Stanley F.</dc:creator>
  <dc:creator>Ozkan, Engin</dc:creator>
  <dc:creator>Kayserili, Hülya</dc:creator>
  <dc:creator>Escande-Beillard, Nathalie</dc:creator>
  <dc:creator>Reversade, Bruno</dc:creator>
  <dc:date>2023-01-01</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/270832</dc:identifier>
  <dc:identifier>oai:aperta.ulakbim.gov.tr:270832</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>EMBO MOLECULAR MEDICINE 15(5) 15</dc:source>
  <dc:title>RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>