SIRT1 Stabilizes PML promoting its Sumoylation
Abstract
SIRT1, the closest mammalian homologue of yeast Sir2, is an NAD+-dependent deacetylase with relevant functions in cancer, aging, and metabolism among other processes. SIRT1 has a diffuse nuclear localization but is recruited to the PML nuclear bodies (PML-NBs) after PML upregulation. However, the functions of SIRT1 in the PML-NBs are unknown. Here, we show that primary mouse embryo fibroblasts lacking SIRT1 contain reduced PML protein levels that are increased after reintroduction of SIRT1. In addition, overexpression of SIRT1 in HEK-293 cells increases the amount of PML protein while knockdown of SIRT1 reduces the size and number of PML-NBs and the levels of PML protein in HeLa cells. SIRT1 stimulates PML sumoylation in vitro and in vivo in a deacetylase-independent manner. Importantly, the absence of SIRT1 reduces the apoptotic response of vesicular stomatitis virus infected cells and favors the extent of this PML sensitive virus replication. These results demonstrate a novel function of SIRT1 in the control of PML and PML-NBs.
| Origin | Files produced by the author(s) |
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