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Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice.
Gerlini, Raffaele; Amendola, Elena; Conte, Andrea; Valente, Valeria; Tornincasa, Mara; Credendino, Sara Carmela; Cammarota, Francesca; Gentile, Chiara; Di Guida, Luigi; Paladino, Simona; De Vita, Gabriella; Fusco, Alfredo; Pierantoni, Giovanna Maria.
Afiliação
  • Gerlini R; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Amendola E; Institute of Experimental Genetics, Helmholtz Zentrum, Munich, Germany.
  • Conte A; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Valente V; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Tornincasa M; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD, USA.
  • Credendino SC; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Cammarota F; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Gentile C; AXXAM S.p.a.-OpenZone, Bresso, Milan, Italy.
  • Di Guida L; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Paladino S; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • De Vita G; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Fusco A; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
  • Pierantoni GM; Department of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, Italy.
Cell Death Dis ; 10(10): 747, 2019 10 03.
Article em En | MEDLINE | ID: mdl-31582725
ABSTRACT
The serine-threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted. About 50% of these Hmga1/Hipk2 double knock-out (DKO) mice die within 12 h of life (P1) for respiratory failure. The DKO mice present an altered lung morphology, likely owing to a drastic reduction in the expression of surfactant proteins, that are required for lung development. Consistently, we report that both HMGA1 and HIPK2 proteins positively regulate the transcriptional activity of the genes encoding the surfactant proteins. Moreover, these mice display an altered expression of thyroid differentiation markers, reasonably because of a drastic reduction in the expression of the thyroid-specific transcription factors PAX8 and FOXE1, which we demonstrate here to be positively regulated by HMGA1 and HIPK2. Therefore, these data indicate a critical role of HIPK2/HMGA1 cooperation in lung and thyroid development and function, suggesting the potential involvement of their impairment in the pathogenesis of human lung and thyroid diseases.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Respiratórias / Glândula Tireoide / Proteínas Serina-Treonina Quinases / Proteína HMGA1a Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Respiratórias / Glândula Tireoide / Proteínas Serina-Treonina Quinases / Proteína HMGA1a Idioma: En Ano de publicação: 2019 Tipo de documento: Article