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p53 and Ceramide as Collaborators in the Stress Response
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236 Riad El Solh, 1107 2020 Beirut, Lebanon
Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236 Riad El Solh, 1107 2020 Beirut, Lebanon
* Author to whom correspondence should be addressed.
Received: 26 December 2012; in revised form: 22 January 2013 / Accepted: 1 February 2013 / Published: 1 March 2013
Abstract: The sphingolipid ceramide mediates various cellular processes in response to several extracellular stimuli. Some genotoxic stresses are able to induce p53-dependent ceramide accumulation leading to cell death. However, in other cases, in the absence of the tumor suppressor protein p53, apoptosis proceeds partly due to the activity of this “tumor suppressor lipid”, ceramide. In the current review, we describe ceramide and its roles in signaling pathways such as cell cycle arrest, hypoxia, hyperoxia, cell death, and cancer. In a specific manner, we are elaborating on the role of ceramide in mitochondrial apoptotic cell death signaling. Furthermore, after highlighting the role and mechanism of action of p53 in apoptosis, we review the association of ceramide and p53 with respect to apoptosis. Strikingly, the hypothesis for a direct interaction between ceramide and p53 is less favored. Recent data suggest that ceramide can act either upstream or downstream of p53 protein through posttranscriptional regulation or through many potential mediators, respectively.
Keywords: ceramide; p53; apoptosis; sphingolipids; mitochondria; signaling; Bcl2 family; caspase
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Hage-Sleiman, R.; Esmerian, M.O.; Kobeissy, H.; Dbaibo, G. p53 and Ceramide as Collaborators in the Stress Response. Int. J. Mol. Sci. 2013, 14, 4982-5012.
Hage-Sleiman R, Esmerian MO, Kobeissy H, Dbaibo G. p53 and Ceramide as Collaborators in the Stress Response. International Journal of Molecular Sciences. 2013; 14(3):4982-5012.
Hage-Sleiman, Rouba; Esmerian, Maria O.; Kobeissy, Hadile; Dbaibo, Ghassan. 2013. "p53 and Ceramide as Collaborators in the Stress Response." Int. J. Mol. Sci. 14, no. 3: 4982-5012.