SUMOylation regulates Rb hyperphosphorylation and inactivation in uveal melanoma |
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Authors: | Fengxi Meng Yiqun Yuan Hui Ren Han Yue Binbin Xu Jiang Qian |
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Affiliation: | 1. Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai China ; 2. Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai China ; 3. NHC Key Laboratory of Myopia, Fudan University, Shanghai China |
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Abstract: | Small ubiquitin‐like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect tumor progression, but the underlying mechanisms remain unclear. Here, we show that, for the first time, in uveal melanoma (UM), the most common intraocular malignancy in adults, global SUMOylation is upregulated and participates in tumor growth. Inhibition of SUMOylation in UM is sufficient to reduce tumor growth both in vitro and in vivo. Furthermore, we found that retinoblastoma protein (Rb) is a target protein and a critical downstream effector of the upregulated SUMOylation activity in UM. Increased SUMOylation of the Rb protein leads to its hyperphosphorylation and inactivation in UM cells, promoting UM cell proliferation. In summary, our results provide novel insight into the mechanism underlying SUMOylation‐regulated tumor growth in UM. |
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Keywords: | ginkgolic acid phosphorylation Rb SUMOylation uveal melanoma |
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