1. SUMOylation of insulin-like growth factor 1 receptor, promotes proliferation in acute myeloid leukemia.
- Author
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Zhang J, Huang FF, Wu DS, Li WJ, Zhan HE, Peng MY, Fang P, Cao PF, Zhang MM, Zeng H, and Chen FP
- Subjects
- Adult, Aged, Apoptosis physiology, Cell Line, Tumor, Cell Proliferation physiology, Female, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Receptor, IGF Type 1 genetics, Signal Transduction, Sumoylation, Young Adult, Leukemia, Myeloid, Acute metabolism, Receptor, IGF Type 1 metabolism
- Abstract
Current valid treatments for acute myeloid leukemia (AML) include chemotherapy and hematopoietic stem cell transplantation, which are defective and limited respectively. The insulin-like growth factor 1 receptor (IGF-1R) is up-regulated in many solid tumors; therefore, it may be a target for tumor therapy. Interestingly, IGF-1R is modified by SUMOylation, a type of reversible post-translational modification. In this study, we found that IGF-1R was increased in both cell lines and clinical samples of AML and was modified by SUMO-1. Furthermore, IGF-1, ligand of IGF-1R, induced the up-regulation of IGF-1R and increased the proliferation of leukemia cell line. After mutation of Lys(1025) and Lys(1100) in IGF-1R, the evolutionarily conserved lysine residues were identified as the SUMOylation sites of IGF-1R, because the SUMOylation of IGF-1R in these mutants was significantly inhibited. Furthermore, the cell proliferation mediated by IGF-1 was also reduced. After inhibition of UBC9, the activating enzyme of SUMOylation, co-expression of IGF-1R and SUMO-1 was down-regulated, and cell proliferation was also inhibited. However, cell apoptosis was not significantly affected. These results suggest that IGF-1R and its SUMOylation may be a new therapeutic target for strategy of AML., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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