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Transcription factor IKZF1 is degraded during the apoptosis of multiple myeloma cells induced by kinase inhibition
Author(s) -
Liu Yaobin,
He Xian,
Sui Yiyan,
Yu Rong,
Xu Guoqiang
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.06.044
Subject(s) - multiple myeloma , ubiquitin , transcription factor , cancer research , bortezomib , proteasome , thalidomide , kinase , pomalidomide , biology , apoptosis , lenalidomide , microbiology and biotechnology , immunology , biochemistry , gene
Immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide exhibit high responsive rates for newly identified or relapsed multiple myeloma patients. However, their mechanisms of action are not completely understood. One mechanism involves the ubiquitination and degradation of two transcription factors, IKZF1 and IKZF3. Whether there are other degradation pathways for IKZF1 in myeloma cells remains unknown. Here, we found that although IKZF1 ubiquitination was reduced, its stability was also significantly reduced in MM1.S and OPM2 cells treated with kinase inhibitors, 5,6‐dichlorobenzimidazole riboside (DRB) or roscovitine. Through pharmacological inhibition and biochemical approaches we demonstrated that instead of undergoing the ubiquitin–proteasome pathway, IKZF1 was degraded through apoptosis induced by kinase inhibition. This result may provide a new direction in developing therapeutic treatments for myeloma patients.