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Start Over Author "Chen, Siquan" Publisher american association for cancer research
4 results on '"Chen, Siquan"'

3. Abstract A70: A genome‐wide siRNA screen for modulators of cell death induced by the proteasome inhibitor bortezomib

Author

Chen, Siquan, primary, Blank, Jonathan L., additional, Peters, Theodore, additional, Liu, Jane, additional, Rappoli, David M., additional, Pickard, Michael D., additional, Menon, Saurabh, additional, Yu, Jie, additional, Driscoll, Denise L., additional, Lingaraj, Trupti, additional, Burkhardt, Anne L., additional, Chen, Wei, additional, Sappal, Darshan S., additional, Gray, Jesse, additional, Garcia, Khristofer, additional, Hales, Paul, additional, Leroy, Patrick J., additional, Ringeling, John, additional, Rabino, Claudia, additional, Spelman, James J., additional, Morgenstern, Jay P., additional, and Lightcap, Eric S., additional

Published
2009
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4. Genome-wide siRNA screen for modulators of cell death induced by proteasome inhibitor bortezomib.

Author

Chen S, Blank JL, Peters T, Liu XJ, Rappoli DM, Pickard MD, Menon S, Yu J, Driscoll DL, Lingaraj T, Burkhardt AL, Chen W, Garcia K, Sappal DS, Gray J, Hales P, Leroy PJ, Ringeling J, Rabino C, Spelman JJ, Morgenstern JP, and Lightcap ES

Subjects
Bortezomib, Cell Death genetics, Colonic Neoplasms drug therapy, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, DNA Damage, Gene Knockdown Techniques, HCT116 Cells, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins genetics, Melanoma drug therapy, Melanoma genetics, Melanoma metabolism, Melanoma pathology, Protein Serine-Threonine Kinases biosynthesis, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins c-myc biosynthesis, Proto-Oncogene Proteins c-myc genetics, Ribosomes drug effects, TOR Serine-Threonine Kinases, Transfection, Antineoplastic Agents pharmacology, Boronic Acids pharmacology, Cell Death drug effects, Protease Inhibitors pharmacology, Proteasome Inhibitors, Pyrazines pharmacology, RNA, Small Interfering genetics
Abstract

Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen to evaluate the genetic determinants that confer sensitivity to bortezomib (Velcade (R); PS-341). This screen identified 100 genes whose knockdown affected lethality to bortezomib and to a structurally diverse set of other proteasome inhibitors. A comparison of three cell lines revealed that 39 of 100 genes were commonly linked to cell death. We causally linked bortezomib-induced cell death to the accumulation of ASF1B, Myc, ODC1, Noxa, BNIP3, Gadd45alpha, p-SMC1A, SREBF1, and p53. Our results suggest that proteasome inhibition promotes cell death primarily by dysregulating Myc and polyamines, interfering with protein translation, and disrupting essential DNA damage repair pathways, leading to programmed cell death., (Copyright 2010 AACR.)

Published
2010
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