Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis
Peng Liao,
Weichao Wang,
Yu Li,
Rui Wang,
Jiali Jin,
Weijuan Pang,
Yunfei Chen,
Mingyue Shen,
Xinbo Wang,
Dongyang Jiang,
Jinjiang Pang,
Mingyao Liu,
Xia Lin,
Xin-Hua Feng,
Ping Wang,
Xin Ge
Affiliations
Peng Liao
Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Weichao Wang
Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Yu Li
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Rui Wang
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Jiali Jin
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Weijuan Pang
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Yunfei Chen
Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
Mingyue Shen
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Xinbo Wang
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Dongyang Jiang
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
Jinjiang Pang
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
Mingyao Liu
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Xia Lin
Department of Surgery, Baylor College of Medicine, Houston, United States
Xin-Hua Feng
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Zhejiang, China
Ping Wang
Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; School of Life Science and Technology, Tongji University, Shanghai, China
SCP1 as a nuclear transcriptional regulator acts globally to silence neuronal genes and to affect the dephosphorylation of RNA Pol ll. However, we report the first finding and description of SCP1 as a plasma membrane-localized protein in various cancer cells using EGFP- or other epitope-fused SCP1. Membrane-located SCP1 dephosphorylates AKT at serine 473, leading to the abolishment of serine 473 phosphorylation that results in suppressed angiogenesis and a decreased risk of tumorigenesis. Consistently, we observed increased AKT phosphorylation and angiogenesis followed by enhanced tumorigenesis in Ctdsp1 (which encodes SCP1) gene - knockout mice. Importantly, we discovered that the membrane localization of SCP1 is crucial for impeding angiogenesis and tumor growth, and this localization depends on palmitoylation of a conserved cysteine motif within its NH2 terminus. Thus, our study discovers a novel mechanism underlying SCP1 shuttling between the plasma membrane and nucleus, which constitutes a unique pathway in transducing AKT signaling that is closely linked to angiogenesis and tumorigenesis.
