American Association for Cancer Research
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Supplementary Figures from SENP1 deSUMOylates and Regulates Pin1 Protein Activity and Cellular Function

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journal contribution
posted on 2023-03-30, 21:22 authored by Chun-Hau Chen, Che-Chang Chang, Tae Ho Lee, ManLi Luo, Pengyu Huang, Pei-Hsin Liao, Shuo Wei, Fu-An Li, Ruey-Hwa Chen, Xiao Zhen Zhou, Hsiu-Ming Shih, Kun Ping Lu

Supplementary Figures - PDF file 635K, Supplementary Figure S1. Pin1 is modified on Lys6 and Lys63 by SUMO1 in vitro and in vivo. Supplementary Figure S2. Pin1 Lys6 and Lys63 mutations increase its ability to active cyclin D1 promoter and stabilize cyclin D1 protein in cells. Supplementary Figure S3. SENP1 binds Pin1 and thereby positively regulates cyclin D1 activation



The Pin1 prolyl isomerase regulates phosphorylation signaling by controlling protein conformation after phosphorylation, and its upregulation promotes oncogenesis via acting on numerous oncogenic molecules. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. However, nothing is known about the role of SUMOylation in regulating Pin1 function. Here, we show that Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain. Pin1 SUMOylation inhibits its protein activity and oncogenic function. We further identify that SENP1 binds to and deSUMOylates Pin1. Importantly, either overexpression of SENP1 or disruption of Pin1 SUMOylation promotes the ability of Pin1 to induce centrosome amplification and cell transformation. Moreover, SENP1 also increases Pin1 protein stability in cell cultures, and Pin1 levels are positively correlated with SENP1 levels in human breast cancer specimens. These results not only uncover Pin1 SUMOylation on Lys6/63 as a novel mechanism to inhibit its activity and function but also identify a critical role for SENP1-mediated deSUMOylation in promoting Pin1 function during tumorigenesis. Cancer Res; 73(13); 3951–62. ©2013 AACR.

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