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Elife. 2017 Mar 31;6. pii: e22058. doi: 10.7554/eLife.22058.

Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis.

Author information

1
Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
2
Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
3
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
4
Department of Surgery, Baylor College of Medicine, Houston, United States.
5
Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Zhejiang, China.
6
School of Life Science and Technology, Tongji University, Shanghai, China.
7
Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

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.

KEYWORDS:

angiogenesis; cancer biology; cell biology; human cancer cell lines; mouse; tumorigenesis

PMID:
28440748
PMCID:
PMC5404917
DOI:
10.7554/eLife.22058
[Indexed for MEDLINE]
Free PMC Article

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