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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{
  "@context": "https://schema.org/", 
  "@id": 270832, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "name": "Wong, Samantha"
    }, 
    {
      "@type": "Person", 
      "affiliation": "ASTAR, Inst Mol & Cellular Biol, Singapore, Singapore", 
      "name": "Tan, Yu Xuan"
    }, 
    {
      "@type": "Person", 
      "name": "Loh, Abigail Yi Ting"
    }, 
    {
      "@type": "Person", 
      "affiliation": "ASTAR, Inst Mol & Cellular Biol, Singapore, Singapore", 
      "name": "Tan, Kiat Yi"
    }, 
    {
      "@type": "Person", 
      "name": "Lee, Hane"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL USA", 
      "name": "Aziz, Zainab"
    }, 
    {
      "@type": "Person", 
      "name": "Nelson, Stanley F."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL USA", 
      "name": "Ozkan, Engin"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Sch Med, Dept Med Genet, Istanbul, Turkiye", 
      "name": "Kayserili, H\u00fclya"
    }, 
    {
      "@type": "Person", 
      "name": "Escande-Beillard, Nathalie"
    }, 
    {
      "@type": "Person", 
      "name": "Reversade, Bruno"
    }
  ], 
  "datePublished": "2023-01-01", 
  "description": "<p>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.</p>", 
  "headline": "RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis", 
  "identifier": 270832, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis", 
  "url": "https://aperta.ulakbim.gov.tr/record/270832"
}