Aurora Kinase A Prevents p53 from Inducing Stem Cell Differentiation

An oncoprotein called aurora kinase A (Aurka) helps maintain embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in the primitive pluripotent state by blocking the action of the tumor suppressor gene p53 that would otherwise induce the stem cells to differentiate.

To determine the mechanism that functions to maintain stem cell status, investigators at Mount Sinai School of Medicine (New York, NY, USA) conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. They reported in the August 3, 2012, issue of the journal Cell Stem Cell that depletion of one such molecule (Aurka), resulted in compromised self-renewal and consequent differentiation.

By integrating global gene expression and computational analyses, they showed that loss of Aurka led to upregulated p53 activity that triggered ESC differentiation. Specifically, Aurka regulated pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impaired p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming.

“These studies are exciting not only from a basic science point-of-view, but also because they suggest that stem cell research may impact the development of novel treatments for cancer. Conversely, cancer research may facilitate the realization of the biomedical potential of stem cells,” said senior author Dr. Ihor Lemischka, professor of developmental and regenerative biology at Mount Sinai School of Medicine.

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