@article{c503852efa2f4836bd5616426f69574c,
title = "Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling",
abstract = "Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming.",
author = "Lee, {Dung Fang} and Jie Su and Ang, {Yen Sin} and Xonia Carvajal-Vergara and Sonia Mulero-Navarro and Pereira, {Carlos F.} and Julian Gingold and Wang, {Hung Liang} and Ruiying Zhao and Ana Sevilla and Henia Darr and Williamson, {Andrew J.K.} and Betty Chang and Xiaohong Niu and Francesca Aguilo and Flores, {Elsa R.} and Sher, {Yuh Pyng} and Hung, {Mien Chie} and Whetton, {Anthony D.} and Gelb, {Bruce D.} and Moore, {Kateri A.} and Snoeck, {Hans Willem} and Avi Ma'Ayan and Christoph Schaniel and Lemischka, {Ihor R.}",
note = "Funding Information: We thank K. Hochedlinger for the Col-SC, Oct4-GFP, and M2rtTA mice. We also thank J. Huang for p53 ChIP-chip data; S.-Y. Tsai and H.L. Xu for useful discussions; and Y. Liu for laboratory management. We also would like to thank S. Ghaffari, M. Rendl, and their laboratories{\textquoteright} assistance. We are grateful to Selleck Chemicals LLC for kindly providing MLN8237, VX-680, and AT-9283. This research was funded by grants from the National Institutes of Health (NIH) to I.R.L. (5R01GM078465), the Empire State Stem Cell Fund through New York State Department of Health (NYSTEM) to I.R.L. (C024176) and to C.S. and I.R.L. (C024410), and Sister Institution Fund of China Medical University and MDACC to M.-C.H. (DOH101-TD-C-005 and NSC-3111-B-039-101). D.-F.L. is a New York Stem Cell Foundation Stanley and Fiona Druckenmiller Fellow; X.C.-V. was a recipient of a Postdoctoral Fellowship from the Ministerio de Ciencia e Innovacion/Instituto de Salud Carlos III, Spain; and C.F.P. is a recipient of an EMBO Long-Term Postdoctoral Fellowship. A.D.W. and A.J.K.W. were recipients of funding from Leukaemia Lymphoma Research. ",
year = "2012",
month = aug,
day = "3",
doi = "10.1016/j.stem.2012.05.020",
language = "English",
volume = "11",
pages = "179--194",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}