Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-). Cell clones (R-WT and R-TSM) expressing equal amounts of IGF1R were selected for experiments. Phosphorylation of IGF-1R, Akt, and Erk upon IGF-1 stimulation was equal in R-WT and R-TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R-WT proliferated substantially faster than R-TSM, which did not differ significantly from the empty vector control. Upon IGF-1 stimulationG1-S-phase progression of R-WT increased from 12 to 38%, compared to 13 to 20% of R-TSM. The G1-S progression of R-WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO-IGF-1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO-IGF-1R dependent mechanisms seem important.
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Calif Pacific Med Ctr, Dept Ophthalmol, Div Oculofacial Plast Surg, San Francisco, CA USACalif Pacific Med Ctr, Dept Ophthalmol, Div Oculofacial Plast Surg, San Francisco, CA USA
Truong, Timothy
Silkiss, Rona Z.
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Calif Pacific Med Ctr, Dept Ophthalmol, Div Oculofacial Plast Surg, San Francisco, CA USA
Silkiss Eye Surg, Dept Ophthalmol, Div Oculofacial Plast Surg, San Francisco, CA USA
Silkiss Eye Surg, 711 Van Ness Ave Suite 340, San Francisco, CA 94102 USACalif Pacific Med Ctr, Dept Ophthalmol, Div Oculofacial Plast Surg, San Francisco, CA USA
机构:
E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Xue, Mengzhu
Cao, Xianwen
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Cao, Xianwen
Zhong, Ye
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Zhong, Ye
Kuang, Dong
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Kuang, Dong
Liu, Xiaofeng
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Liu, Xiaofeng
Zhao, Zhenjiang
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China
Zhao, Zhenjiang
Li, Honglin
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E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China