The Six1 oncoprotein represses translation of P53 via concomitant regulation of RPL26 and microRNA-27a
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TP53 is described as the “guardian of the genome” due to its critical role in mediating DNA damage-induced cell cycle arrest and apoptosis. While TP53 is mutated in 50% of all cancers, its function is also thought to be compromised in many cancers where it is not mutated. Our data demonstrate that the homeoprotein Six1, which is overexpressed in numerous tumor types, decreases the levels of wild type p53 through a mechanism that does not involve the well-known negative regulator of p53, MDM2, or any other ubiquitin ligase that influences p53 degradation. Similarly, other known oncogenic pathways ...