Journalartikel
Autorenliste: Tang, Shuang; Huang, Gang; Fan, Wei; Chen, Yue; Ward, James M.; Xu, Xiaojiang; Xu, Qing; Kang, Ashley; McBurney, Michael W.; Fargo, David C.; Hu, Guang; Baumgart-Vogt, Eveline; Zhao, Yingming; Li, Xiaoling
Jahr der Veröffentlichung: 2014
Seiten: 843-855
Zeitschrift: Molecular Cell
Bandnummer: 55
Heftnummer: 6
ISSN: 1097-2765
eISSN: 1097-4164
Open Access Status: Green
DOI Link: https://doi.org/10.1016/j.molcel.2014.07.011
Verlag: Cell Press
Abstract:
Retinoid homeostasis is critical for normal embryonic development. Both the deficiency and excess of these compounds are associated with congenital malformations. Here we demonstrate that SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, contributes to homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation in part through deacetylation of cellular retinoic acid binding protein II (CRABPII). We show that RA-mediated acetylation of CRABPII at K102 is essential for its nuclear accumulation and subsequent activation of RA signaling. SIRT1 interacts with and deacetylates CRABPII, regulating its subcellular localization. Consequently, SIRT1 deficiency induces hyperacetylation and nuclear accumulation of CRABPII, enhancing RA signaling and accelerating mESC differentiation in response to RA. Consistently, SIRT1 deficiency is associated with elevated RA signaling and development defects in mice. Our findings reveal a molecular mechanism that regulates RA signaling and highlight the importance of SIRT1 in regulation of ESC pluripotency and embryogenesis.
Zitierstile
Harvard-Zitierstil: Tang, S., Huang, G., Fan, W., Chen, Y., Ward, J., Xu, X., et al. (2014) SIRT1-Mediated Deacetylation of CRABPII Regulates Cellular Retinoic Acid Signaling and Modulates Embryonic Stem Cell Differentiation, Molecular Cell, 55(6), pp. 843-855. https://doi.org/10.1016/j.molcel.2014.07.011
APA-Zitierstil: Tang, S., Huang, G., Fan, W., Chen, Y., Ward, J., Xu, X., Xu, Q., Kang, A., McBurney, M., Fargo, D., Hu, G., Baumgart-Vogt, E., Zhao, Y., & Li, X. (2014). SIRT1-Mediated Deacetylation of CRABPII Regulates Cellular Retinoic Acid Signaling and Modulates Embryonic Stem Cell Differentiation. Molecular Cell. 55(6), 843-855. https://doi.org/10.1016/j.molcel.2014.07.011
Schlagwörter
BINDING PROTEIN-II; CDX1; MUTANT MICE; NUCLEAR RECEPTORS; RESTRICTION; SIRT1
