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Int. J. Mol. Sci. 2013, 14(8), 15260-15285; doi:10.3390/ijms140815260

The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence

Experimental Dermatology, Department of Dermatology, TU Dresden, 01307 Dresden, Germany
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Received: 17 June 2013 / Revised: 27 June 2013 / Accepted: 1 July 2013 / Published: 24 July 2013
(This article belongs to the Collection Radiation Toxicity in Cells)
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Abstract

Induction of DNA damage by UVB and UVA radiation may generate mutations and genomic instability leading to carcinogenesis. Therefore, skin cells being repeatedly exposed to ultraviolet (UV) light have acquired multilayered protective mechanisms to avoid malignant transformation. Besides extensive DNA repair mechanisms, the damaged skin cells can be eliminated by induction of apoptosis, which is mediated through the action of tumor suppressor p53. In order to prevent the excessive loss of skin cells and to maintain the skin barrier function, apoptotic pathways are counteracted by anti-apoptotic signaling including the AKT/mTOR pathway. However, AKT/mTOR not only prevents cell death, but is also active in cell cycle transition and hyper-proliferation, thereby also counteracting p53. In turn, AKT/mTOR is tuned down by the negative regulators being controlled by the p53. This inhibition of AKT/mTOR, in combination with transactivation of damage-regulated autophagy modulators, guides the p53-mediated elimination of damaged cellular components by autophagic clearance. Alternatively, p53 irreversibly blocks cell cycle progression to prevent AKT/mTOR-driven proliferation, thereby inducing premature senescence. Conclusively, AKT/mTOR via an extensive cross talk with p53 influences the UV response in the skin with no black and white scenario deciding over death or survival. View Full-Text
Keywords: UV; DNA damage; p53; AKT; mTOR; cell death; apoptosis; autophagy; senescence; heat shock UV; DNA damage; p53; AKT; mTOR; cell death; apoptosis; autophagy; senescence; heat shock
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Strozyk, E.; Kulms, D. The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence. Int. J. Mol. Sci. 2013, 14, 15260-15285.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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