LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during Liver Regeneration
| Autor: | Maillet, Vanessa, Boussetta, Nadia, Leclerc, Jocelyne, Fauveau, Veronique, Foretz, Marc, Viollet, Benoit, Couty, Jean-Pierre, Celton-Morizur, Séverine, Perret, Christine, Desdouets, Chantal |
|---|---|
| Přispěvatelé: | Viollet, Benoit, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), This study was supported by grants from INSERM, Agence Nationale de la Recherche (ANR-2010-BLANC-1123-02). V.M. was a recipient of a La Ligue Nationale Contre le Cancer (LNCC) grant. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
MESH: Signal Transduction
congenital hereditary and neonatal diseases and abnormalities MESH: Enzyme Activation LKB1 EGFR Mitosis AMP-Activated Protein Kinases Protein Serine-Threonine Kinases MESH: ErbB Receptors MESH: Protein-Serine-Threonine Kinases MESH: Hepatocytes Mice MESH: Ploidies MESH: Cell Proliferation Animals MESH: Animals MESH: Gene Silencing MESH: Genome Gene Silencing skin and connective tissue diseases liver regeneration lcsh:QH301-705.5 MESH: Mice polyploidy Cell Proliferation [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Genome Ploidies MESH: Mitosis [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Enzyme Activation ErbB Receptors Liver lcsh:Biology (General) MESH: Gene Deletion hepatocytes MESH: Liver Regeneration microtubule spindle mitosis fidelity Gene Deletion Signal Transduction MESH: Liver |
| Zdroj: | Cell Reports Cell Reports, 2018, 22 (8), pp.1994-2005. ⟨10.1016/j.celrep.2018.01.086⟩ Cell Reports, Vol 22, Iss 8, Pp 1994-2005 (2018) Cell Reports, Elsevier Inc, 2018, 22 (8), pp.1994-2005. ⟨10.1016/j.celrep.2018.01.086⟩ |
| ISSN: | 2211-1247 |
| Popis: | Comment inLKB1: Controlling Quiescence and Genomic Integrity at Home. [Trends Endocrinol Metab. 2018]; International audience; Liver kinase B1 (LKB1) is involved in several biological processes and is a key regulator of hepatic metabolism and polarity. Here, we demonstrate that the master kinase LKB1 plays a dual role in liver regeneration, independently of its major target, AMP-activated protein kinase (AMPK). We found that the loss of hepatic Lkb1 expression promoted hepatocyte proliferation acceleration independently of metabolic/energetic balance. LKB1 regulates G0/G1 progression, specifically by controlling epidermal growth factor receptor (EGFR) signaling. Furthermore, later in regeneration, LKB1 controls mitotic fidelity. The deletion of Lkb1 results in major alterations to mitotic spindle formation along the polarity axis. Thus, LKB1 deficiency alters ploidy profile at late stages of regeneration. Our findings highlight the dual role of LKB1 in liver regeneration, as a guardian of hepatocyte proliferation and genomic integrity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|