The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis

Autor: Raphael G. P. Denis, Leila Maouche-Chretien, Marine Granger-Locatelli, Cécile Badoual, Suthat Fucharoen, Stany Chrétien, Philippe Leboulch, Serge Luquet, Olivier Goupille, Tipparat Penglong, Zahra Kadri
Přispěvatelé: Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Mahidol University [Bangkok], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ORANGE, Colette
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports
Cell Reports, 2017, 21 (12), pp.3524-3535. ⟨10.1016/j.celrep.2017.11.098⟩
Cell Reports, Elsevier Inc, 2017, 21 (12), pp.3524-3535. ⟨10.1016/j.celrep.2017.11.098⟩
Cell Reports, Vol 21, Iss 12, Pp 3524-3535 (2017)
ISSN: 2211-1247
Popis: Summary: GATA transcription factors and their FOG cofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOG factors. We recently demonstrated that interactions between retinoblastoma protein (pRb) and GATA-1 are crucial for erythroid proliferation and differentiation. We show here that the LXCXE pRb-binding site of FOG-2 is involved in adipogenesis. Unlike GATA-1, which inhibits cell division, FOG-2 promotes proliferation. Mice with a knockin of a Fog2 gene bearing a mutated LXCXE pRb-binding site are resistant to obesity and display higher rates of white-to-brown fat conversion. Thus, each component of the GATA/FOG complex (GATA-1 and FOG-2) is involved in pRb/E2F regulation, but these molecules have markedly different roles in the control of tissue homeostasis. : Goupille et al. find that a mutation of the FOG-2 LXCXE pRb-binding site decreases cell proliferation and affects adipogenesis in vitro and in vivo. Fog2Rb−/Rb− mutant mice are resistant to obesity, and they present abnormal WAT/BAT conversion and lactate production. Oxamate treatment results in phenotype reversion in these mice. Keywords: FOG-2, GATA, retinoblastoma, WAT, BAT, adipogenesis, obesity
Databáze: OpenAIRE