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Sustained protein synthesis and reduced eEF2K levels in TAp73<sup>-\-</sup> mice brain : a possible compensatory mechanism

Sustained protein synthesis and reduced eEF2K levels in TAp73-\- mice brain : a possible compensatory mechanism

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ROTBLAT, Barak, Massimiliano AGOSTINI, Maria Victoria NIKLISON-CHIROU, Ivano AMELIO, Anne E. WILLIS, Gerry MELINO, 2018. Sustained protein synthesis and reduced eEF2K levels in TAp73-\- mice brain : a possible compensatory mechanism. In: Cell Cycle. Taylor & Francis. 17(23), pp. 2637-2643. ISSN 1538-4101. eISSN 1551-4005. Available under: doi: 10.1080/15384101.2018.1553341

@article{Rotblat2018Susta-56666, title={Sustained protein synthesis and reduced eEF2K levels in TAp73-\- mice brain : a possible compensatory mechanism}, year={2018}, doi={10.1080/15384101.2018.1553341}, number={23}, volume={17}, issn={1538-4101}, journal={Cell Cycle}, pages={2637--2643}, author={Rotblat, Barak and Agostini, Massimiliano and Niklison-Chirou, Maria Victoria and Amelio, Ivano and Willis, Anne E. and Melino, Gerry} }

2018 Agostini, Massimiliano Amelio, Ivano Niklison-Chirou, Maria Victoria Niklison-Chirou, Maria Victoria Rotblat, Barak 2022-02-23T13:44:21Z terms-of-use Melino, Gerry Amelio, Ivano Willis, Anne E. 2022-02-23T13:44:21Z Willis, Anne E. Agostini, Massimiliano eng The transcription factor p73 is a member of the p53 family, of which the transactivation domain containing isoform (TAp73) plays key roles in brain development and neuronal stem cells. TAp73 also facilitates homoeostasis and prevents oxidative damage in vivo by inducing the expression of its target genes. Recently, we found that in addition to its role in regulation of transcription, TAp73 also affects mRNA translation. In cultured cells, acute TAp73 depletion activates eEF2K, which phosphorylates eEF2 reducing mRNA translation elongation. As a consequence, there is a reduction in global proteins synthesis rates and reprogramming of the translatome, leading to a selective decrease in the translation of rRNA processing factors. Given the dramatic effects of Tap73 depletion in vitro it was important to determine whether similar effects were observed in vivo. Here, we report the surprising finding that in brains of TAp73 KO mice there is a reduced level of eEF2K, which allows protein synthesis rates to be maintained suggesting a compensation model. These data provide new insights to the role of TAp73 in translation regulation and the eEF2K pathway in the brain. Melino, Gerry Sustained protein synthesis and reduced eEF2K levels in TAp73<sup>-\-</sup> mice brain : a possible compensatory mechanism Rotblat, Barak

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