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|Title:||Ribosomal protein S6 kinase 1 promotes the survival of photoreceptors in retinitis pigmentosa||Authors:||Lin, B
|Issue Date:||2018||Publisher:||Nature Publishing Group||Source:||Cell death & disease, Nov. 2018, v. 9, 1141, p. 1-14 How to cite?||Journal:||Cell death & disease||Abstract:||Retinitis pigmentosa (RP) is a heterogeneous group of inherited disorders caused by mutations in genes that are mostly expressed by rod photoreceptors, which results in initial death of rods followed by cone photoreceptors. The molecular mechanisms that lead to both rod and cone degeneration are not yet fully understood. The mTOR pathway is implicated in RP. However, it remains unclear whether S6K1 plays an essential role downstream of the mTOR pathway in mediating photoreceptor survival in RP. Our in vitro studies demonstrated that PTEN (phosphatase and tensin homolog) overexpression deactivated mTOR activity and induced 661W cone cell apoptosis. In addition, we identified that S6K1 but not 4EBP1 was the downstream effector of PTEN neurotoxicity using gain-and loss-of-function approaches. Moreover, our in vivo data corroborated the results of our in vitro studies. S6K1 overexpression either in rods or cones promoted these cell survival and function and improved visual performance in the rd10 mouse model of RP. Our data demonstrated that S6K1 was the downstream effector of mTOR and that S6K1 was critical for both rod and cone survival in RP. Our findings make a strong case for targeting S6K1 as a promising therapeutic strategy for promoting the survival of photoreceptors in RP.||URI:||http://hdl.handle.net/10397/80292||ISSN:||2041-4889||DOI:||10.1038/s41419-018-1198-1||Rights:||© The Author(s) 2018
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The following publication Lin, B., Xiong, G.Y., & Yang, W. (2018). Ribosomal protein S6 kinase 1 promotes the survival of photoreceptors in retinitis pigmentosa. Cell death & disease, 9, 1141, 1-14 is available at https://dx.doi.org/10.1038/s41419-018-1198-1
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