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

Willis, Anne E.; Rotblat, Barak; Agostini, Massimiliano; Amelio, Ivano; Niklison-Chirou, Maria Victoria; Melino, Gerry

Abstract

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.

Citation

Willis, A. E., Rotblat, B., Agostini, M., Amelio, I., Niklison-Chirou, M. V., & Melino, G. (2018). Sustained protein synthesis and reduced eEF2K levels in TAp73-\- mice brain: a possible compensatory mechanism. Cell Cycle, 17(23), 2637-2643. https://doi.org/10.1080/15384101.2018.1553341

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2018
• Online Publication Date: Dec 4, 2018
• Publication Date: Dec 2, 2018
• Deposit Date: Mar 31, 2020
• Journal: Cell Cycle
• Print ISSN: 1538-4101
• Electronic ISSN: 1551-4005
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 23
• Pages: 2637-2643
• DOI: https://doi.org/10.1080/15384101.2018.1553341
• Keywords: Developmental Biology; Cell Biology; Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4234773
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/15384101.2018.1553341
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=kccy20; Received: 2018-09-11; Revised: 2018-10-26; Accepted: 2018-11-15; Published: 2018-12-03