Quantitative proteomic analysis to decipher the differential apoptotic response of bortezomib-treated APL cells before and after retinoic acid differentiation reveals involvement of protein toxicity mechanisms.
Cell biology; iTRAQ; Kinetic of protein variation; Proteasome inhibition
Abstract :
[en] The ubiquitin-proteasome system allows the targeted degradation of proteins and plays a critical role in the regulation of many cellular processes. Proteasome inhibition is a recent antitumor therapeutic strategy and bortezomib was the first proteasome inhibitor approved for clinical use. In this study, we used the NB4 cell line to investigate the effects of bortezomib toward acute promyelocytic leukemia cells before and after retinoic acid-induced differentiation. We showed that apoptosis level after bortezomib treatment is higher in NB4 cells than in differentiated NB4 cells. To compare early protein variations upon bortezomib treatment in both NB4 cell populations, we performed a quantitative proteomic analysis based on iTRAQ peptide labeling followed by data analysis with in-house developed scripts. This strategy revealed the regulation of 14 proteins principally involved in protein stress response and apoptosis in NB4 cells after proteasome inhibition. Altogether, our results suggest that the differential level of apoptosis induced by bortezomib treatment in both NB4 cell populations could result from distinct protein toxicity level.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Uttenweiler-Joseph, Sandrine; Universite de Toulouse, UPS, IPBS, Toulouse, France > CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
Bouyssié, David; Universite de Toulouse, UPS, IPBS, Toulouse, France > CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
Calligaris, David ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
Lutz, Pierre G.; Universite de Toulouse, UPS, IPBS, Toulouse, France > CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
Monsarrat, Bernard; Universite de Toulouse, UPS, IPBS, Toulouse, France > CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
Burlet-Schiltz, Odile; Universite de Toulouse, UPS, IPBS, Toulouse, France > CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
Language :
English
Title :
Quantitative proteomic analysis to decipher the differential apoptotic response of bortezomib-treated APL cells before and after retinoic acid differentiation reveals involvement of protein toxicity mechanisms.
Hoeller, D., Dikic, I., Targeting the ubiquitin system in cancer therapy. Nature 2009, 458, 438-444.
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S. et al., A phase 2 study of bortezomib in relapsed, refractory myeloma. New Engl. J. Med. 2003, 348, 2609-2617.
Fisher, R. I., Bernstein, S. H., Kahl, B. S., Djulbegovic, B. et al., Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J. Clin. Oncol.2006, 24, 4867-4874.
Ruschak, A. M., Slassi, M., Kay, L. E., Schimmer, A. D., Novel proteasome inhibitors to overcome bortezomib resistance. J. Natl. Cancer Inst. 2011, 103, 1007-1017.
Dick, L. R., Fleming, P. E., Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov. Today 2010, 15, 243-249.
McConkey, D. J., Zhu, K., Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist. Updat. 2008, 11, 164-179.
Mitsiades, N., Mitsiades, C. S., Poulaki, V., Chauhan, D. et al., Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 14374-14379.
Bieler, S., Meiners, S., Stangl, V., Pohl, T. et al., Comprehensive proteomic and transcriptomic analysis reveals early induction of a protective anti-oxidative stress response by low-dose proteasome inhibition. Proteomics 2009, 9, 3257-3267.
Zhang, L., Chang, M., Li, H., Hou, S. et al., Proteomic changes of PC12 cells treated with proteasomal inhibitor PSI. Brain Res. 2007, 1153, 196-203.
Weinkauf, M., Zimmermann, Y., Hartmann, E., Rosenwald, A. et al., 2-D PAGE-based comparison of proteasome inhibitor bortezomib in sensitive and resistant mantle cell lymphoma. Electrophoresis 2009, 30, 974-986.
Hideshima, T., Richardson, P., Chauhan, D., Palombella, V. J. et al., The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001, 61, 3071-3076.
Drexler, H. C., Activation of the cell death program by inhibition of proteasome function. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 855-860.
Lanotte, M., Martin-Thouvenin, V., Najman, S., Balerini, P. et al., NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood 1991, 77, 1080-1086.
Taimi, M., Breitman, T. R., Growth, differentiation, and death of retinoic acid-treated human acute promyelocytic leukemia NB4 cells. Exp. Cell Res. 1997, 230, 69-75.
Bouyssie, D., Gonzalez de Peredo, A., Mouton, E., Albigot, R. et al., Mascot file parsing and quantification (MFPaQ), a new software to parse, validate, and quantify proteomics data generated by ICAT and SILAC mass spectrometric analyses: application to the proteomics study of membrane proteins from primary human endothelial cells. Mol. Cell. Proteomics 2007, 6, 1621-1637.
Matondo, M., Bousquet-Dubouch, M. P., Gallay, N., Uttenweiler-Joseph, S. et al., Proteasome inhibitor-induced apoptosis in acute myeloid leukemia: a correlation with the proteasome status. Leuk. Res. 2010, 34, 498-506.
Navarro, P., Vazquez, J., A refined method to calculate false discovery rates for peptide identification using decoy databases. J. Proteome Res. 2009, 8, 1792-1796.
Riccioni, R., Senese, M., Diverio, D., Riti, V. et al., M4 and M5 acute myeloid leukaemias display a high sensitivity to Bortezomib-mediated apoptosis. Br. J. Haematol. 2007, 139, 194-205.
Colado, E., Alvarez-Fernandez, S., Maiso, P., Martin-Sanchez, J. et al., The effect of the proteasome inhibitor bortezomib on acute myeloid leukemia cells and drug resistance associated with the CD34+ immature phenotype. Haematologica 2008, 93, 57-66.
Kamimura, T., Miyamoto, T., Harada, M., Akashi, K., Advances in therapies for acute promyelocytic leukemia. Cancer Sci. 2011, 102, 1929-1937.
Rodriguez-Suarez, E., Gubb, E., Alzueta, I. F., Falcon-Perez, J. M. et al., Virtual expert mass spectrometrist: iTRAQ tool for database-dependent search, quantitation and result storage. Proteomics 2010, 10, 1545-1556.
Lin, W. T., Hung, W. N., Yian, Y. H., Wu, K. P. et al., Multi-Q: a fully automated tool for multiplexed protein quantitation. J. Proteome Res. 2006, 5, 2328-2338.
Kuzyk, M. A., Ohlund, L. B., Elliott, M. H., Smith, D. et al., A comparison of MS/MS-based, stable-isotope-labeled, quantitation performance on ESI-quadrupole TOF and MALDI-TOF/TOF mass spectrometers. Proteomics 2009, 9, 3328-3340.
Bauer, C., Kleinjung, F., Ruthishauser, D., Panse, C. et al., PPINGUIN: peptide profiling guided identification of proteins improves quantitation of iTRAQ ratios. BMC Bioinformatics 2012, 13, 34.
Wang, D., Jensen, R., Gendeh, G., Williams, K. et al., Proteome and transcriptome analysis of retinoic acid-induced differentiation of human acute promyelocytic leukemia cells, NB4. J. Proteome Res. 2004, 3, 627-635.
Zheng, P. Z., Wang, K. K., Zhang, Q. Y., Huang, Q. H. et al., Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 7653-7658.
Wagner, S. A., Beli, P., Weinert, B. T., Nielsen, M. L. et al., A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol. Cell. Proteomics 2011, 10, M111 013284.
Wu, W. K., Cho, C. H., Lee, C. W., Wu, K. et al., Proteasome inhibition: a new therapeutic strategy to cancer treatment. Cancer Lett. 2010, 293, 15-22.
Tourriere, H., Chebli, K., Zekri, L., Courselaud, B. et al., The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 2003, 160, 823-831.
Buchan, J. R., Parker, R., Eukaryotic stress granules: the ins and outs of translation. Mol. Cell 2009, 36, 932-941.
Fournier, M. J., Gareau, C., Mazroui, R., The chemotherapeutic agent bortezomib induces the formation of stress granules. Cancer Cell Int. 2010, 10, 12.
Schuberth, C., Buchberger, A., UBX domain proteins: major regulators of the AAA ATPase Cdc48/p97. Cell. Mol. Life Sci. 2008, 65, 2360-2371.
Malhotra, J. D., Kaufman, R. J., The endoplasmic reticulum and the unfolded protein response. Semin. Cell Dev. Biol. 2007, 18, 716-731.
Schroder, M., Kaufman, R. J., The mammalian unfolded protein response. Annu. Rev. Biochem. 2005, 74, 739-789.
Obeng, E. A., Carlson, L. M., Gutman, D. M., Harrington, W. J., Jr. et al., Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 2006, 107, 4907-4916.
Kothakota, S., Azuma, T., Reinhard, C., Klippel, A. et al., Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 1997, 278, 294-298.
Gu, Y., Filippi, M. D., Cancelas, J. A., Siefring, J. E. et al., Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 2003, 302, 445-449.
Wong, C. H., Chan, H., Ho, C. Y., Lai, S. K. et al., Apoptotic histone modification inhibits nuclear transport by regulating RCC1. Nat. Cell Biol. 2009, 11, 36-45.
Ferrando-May, E., Nucleocytoplasmic transport in apoptosis. Cell Death Differ. 2005, 12, 1263-1276.
Williams, D., Norman, G., Khoury, C., Metcalfe, N. et al., Evidence for a second messenger function of dUTP during Bax mediated apoptosis of yeast and mammalian cells. Biochim. Biophys. Acta 2011, 1813, 315-321.
Lim, L. H., Pervaiz, S., Annexin 1: the new face of an old molecule. FASEB J. 2007, 21, 968-975.
Kang, J. H., Li, M., Chen, X., Yin, X. M., Proteomics analysis of starved cells revealed Annexin A1 as an important regulator of autophagic degradation. Biochem. Biophys. Res. Commun. 2011, 407, 581-586.
Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C., Rubinsztein, D. C., Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 2010, 12, 747-757.
Wu, W. K., Sakamoto, K. M., Milani, M., Aldana-Masankgay, G. et al., Macroautophagy modulates cellular response to proteasome inhibitors in cancer therapy. Drug Resist. Updat. 2010, 13, 87-92.
Belloni, D., Veschini, L., Foglieni, C., Dell'Antonio, G. et al., Bortezomib induces autophagic death in proliferating human endothelial cells. Exp. Cell Res. 2010, 316, 1010-1018.
Kopito, R. R., Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000, 10, 524-530.
Bennett, E. J., Bence, N. F., Jayakumar, R., Kopito, R. R., Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol. Cell 2005, 17, 351-365.
Garcia-Mata, R., Gao, Y. S., Sztul, E., Hassles with taking out the garbage: aggravating aggresomes. Traffic 2002, 3, 388-396.
Isakson, P., Bjoras, M., Boe, S. O., Simonsen, A., Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood 2010, 116, 2324-2331.
Trocoli, A., Mathieu, J., Priault, M., Reiffers, J. et al., ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells. Autophagy 2011, 7, 1108-1114.
Tabas, I., Ron, D., Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 2011, 13, 184-190.
Eisenberg-Lerner, A., Bialik, S., Simon, H. U., Kimchi, A., Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009, 16, 966-975.
Neznanov, N., Komarov, A. P., Neznanova, L., Stanhope-Baker, P., Gudkov, A. V., Proteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib. Oncotarget 2011, 2, 209-221.
Hideshima, T., Bradner, J. E., Wong, J., Chauhan, D. et al., Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 8567-8572.
Kawaguchi, T., Miyazawa, K., Moriya, S., Ohtomo, T. et al., Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk among proteasome, autophagy-lysosome and ER stress. Int. J. Oncol. 2011, 38, 643-654.