The small heat shock protein B8 (HSPB8) confers resistance to bortezomib by promoting autophagic removal of misfolded proteins in multiple myeloma cells
作者： Mohamed-Amine Hamouda , Nathalie Belhacene , Alexandre Puissant , Pascal Colosetti , Guillaume Robert
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摘要: Velcade is one of the inescapable drug to treat patient suffering from multiple myeloma (MM) and resistance this represents a major drawback for patients. However, mechanisms underlying velcade remain incompletely understood. We derived several U266 MM cell clones that resist velcade. U266-resistant cells were resistant velcade-induced death but exhibited similar sensitivity various proapoptotic stimuli. Careful analysis proteosomal subunits proteasome enzymatic activities showed neither composition nor activity was affected in velcade-resistant cells. Elimination poly-ubiquitinated proteins protein aggregates drastically stimulated correlated with increased survival. Inhibition lysosomal resulted an increase decrease survival, indicating are eliminated through degradation. In addition, pangenomic profiling velcade-sensitive small heat shock HSPB8 overexpressed Finally, gain loss function experiment demonstrated key factor resistance. conclusion, plays important role elimination contributes their enhanced
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Rickard Glas, Matthew Bogyo, John S. McMaster, Maria Gaczynska, Hidde L. Ploegh, A proteolytic system that compensates for loss of proteasome function Nature. ,vol. 392, pp. 618- 622 ,(1998) , 10.1038/33443
R.C. Sharma, S Inoue, J Roitelman, R.T. Schimke, R.D. Simoni, Peptide transport by the multidrug resistance pump. Journal of Biological Chemistry. ,vol. 267, pp. 5731- 5734 ,(1992) , 10.1016/S0021-9258(18)42611-7
Teru Hideshima, Klaus Podar, Reshma Shringarpure, Dharminder Chauhan, Kenneth C Anderson, Guilan Li, Yasuyuki Ohtake, Blockade of Hsp27 Overcomes Bortezomib/Proteasome Inhibitor PS-341 Resistance in Lymphoma Cells Cancer Research. ,vol. 63, pp. 6174- 6177 ,(2003)
W M Gregory, M A Richards, J S Malpas, Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. Journal of Clinical Oncology. ,vol. 10, pp. 334- 342 ,(1992) , 10.1200/JCO.1992.10.2.334
Deborah Ricci, Dixie-Lee Esseltine, William L. Trepicchio, George Mulligan, Kenneth C. Anderson, David I. Lichter, Hadi Danaee, Michael D. Pickard, Olga Tayber, Michael Sintchak, Hongliang Shi, Paul G. Richardson, Jamie Cavenagh, Joan Bladé, Thierry Façon, Ruben Niesvizky, Melissa Alsina, William Dalton, Pieter Sonneveld, Sagar Lonial, Helgi van de Velde, Sequence analysis of β-subunit genes of the 20S proteasome in patients with relapsed multiple myeloma treated with bortezomib or dexamethasone. Blood. ,vol. 120, pp. 4513- 4516 ,(2012) , 10.1182/BLOOD-2012-05-426924
Paul G. Richardson, Constantine Mitsiades, Teru Hideshima, Kenneth C. Anderson, Proteasome inhibition in the treatment of cancer. Cell Cycle. ,vol. 4, pp. 290- 296 ,(2005) , 10.4161/CC.4.2.1414
Michel Attal, Jean-Luc Harousseau, Thierry Facon, François Guilhot, Chantal Doyen, Jean-Gabriel Fuzibet, Mathieu Monconduit, Cyrille Hulin, Denis Caillot, Reda Bouabdallah, Laurent Voillat, Jean-Jacques Sotto, Bernard Grosbois, Regis Bataille, Single versus Double Autologous Stem-Cell Transplantation for Multiple Myeloma New England Journal of Medicine. ,vol. 349, pp. 2495- 2502 ,(2003) , 10.1056/NEJMOA032290
Kenneth L Rock, Ian A York, Alfred L Goldberg, Post-proteasomal antigen processing for major histocompatibility complex class I presentation Nature Immunology. ,vol. 5, pp. 670- 677 ,(2004) , 10.1038/NI1089
Lisa J.A. Crawford, Brian Walker, Huib Ovaa, Dharminder Chauhan, Kenneth C. Anderson, Treen C.M. Morris, Alexandra E. Irvine, Comparative Selectivity and Specificity of the Proteasome Inhibitors BzLLLCOCHO, PS-341, and MG-132 Cancer Research. ,vol. 66, pp. 6379- 6386 ,(2006) , 10.1158/0008-5472.CAN-06-0605
Ruud Oerlemans, Niels E. Franke, Yehuda G. Assaraf, Jacqueline Cloos, Ina van Zantwijk, Celia R. Berkers, George L. Scheffer, Kabir Debipersad, Katharina Vojtekova, Clara Lemos, Joost W. van der Heijden, Bauke Ylstra, Godefridus J. Peters, Gertjan L. Kaspers, Ben A. C. Dijkmans, Rik J. Scheper, Gerrit Jansen, Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein Blood. ,vol. 112, pp. 2489- 2499 ,(2008) , 10.1182/BLOOD-2007-08-104950