| First Author | Liao P | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28440748 | Mgi Jnum | J:257145 |
| Mgi Id | MGI:6116991 | Doi | 10.7554/eLife.22058 |
| Citation | Liao P, et al. (2017) Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis. Elife 6:e22058 |
| abstractText | 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. |
