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|Prohibitin deficiency blocks proliferation and induces apoptosis in human hepatoma cells: molecular mechanisms and functional implications|
|Authors: ||Sanchez-Quiles, V. (Virginia)|
Santamaria, E. (Enrique)
Segura, V. (Víctor)
Sesma, L. (Laura)
Prieto, J. (Jesús)
Corrales, F.J. (Fernando José)
|Issue Date: ||2010|
|Publisher: ||Wiley-VCH Verlag Berlin|
|Publisher version: ||http://onlinelibrary.wiley.com/doi/10.1002/pmic.200900757/abstract|
|Citation: ||Sanchez-Quiles V, Santamaria E, Segura V, Sesma L, Prieto J, Corrales FJ. Prohibitin deficiency blocks proliferation and induces apoptosis in human hepatoma cells: molecular mechanisms and functional implications. Proteomics 2010 Apr;10(8):1609-1620.|
Prohibitin is a multifunctional protein participating in a plethora of essential cellular functions, such as cell signaling, apoptosis, survival and proliferation. In the liver, deficient prohibitin activity participates in the progression of non-alcoholic steatohepatitis and obesity, according to mechanisms that still must be elucidated. In this study, we have used a combination of transcriptomics and proteomics technologies to investigate the response of human hepatoma PLC/PRF/5 cells to prohibitin silencing to define in detail the biological function of hepatic Phb1 and to elucidate potential prohibitin-dependent mechanisms participating in the maintenance of the transformed phenotype. Abrogation of prohibitin reduced proliferation and induced apoptosis in human hepatoma cells in a mechanism dependent on NF kappaB signaling. Moreover, down-regulation of ERp29 together with down-regulation of Erlin 2 suggests ER stress. In agreement, increased C/EBP homologous protein levels, poly-ADP ribose polymerase cleavage and activation of caspase 12 and downstream caspase 7 evidenced ER stress-induced apoptosis. Down-regulation of proteasome activator complex subunit 2 and stathmin as well as accumulation of ubiquitinated proteins suggest interplay between ER stress and proteasome malfunction. Taken together, our results provide evidences for prohibitin having a central role in the maintenance of the transformed and invasive phenotype of human hepatoma cells and may further support previous studies suggesting prohibitin as a potential clinical target.
|Permanent link: ||http://hdl.handle.net/10171/21553|
|Appears in Collections:||DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista|
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista
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