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Infection Reveals a Modification of SIRT2 Critical for Chromatin Association.

ABSTRACT: Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translational modification sites and focus on serine 25 phosphorylation. We show that infection specifically induces dephosphorylation of S25, an event essential for SIRT2 chromatin association. Furthermore, we identify a nuclear complex formed by the phosphatases PPM1A and PPM1B, with SIRT2 essential for controlling H3K18 deacetylation and SIRT2-mediated gene repression during infection and necessary for a productive Listeria infection. This study reveals a molecular mechanism regulating SIRT2 function and localization, paving the way for understanding other SIRT2-regulated cellular processes.

SUBMITTER: Pereira JM

PROVIDER: S-EPMC5946459 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Infection Reveals a Modification of SIRT2 Critical for Chromatin Association.

Pereira Jorge M JM Chevalier Christine C Chaze Thibault T Gianetto Quentin Q Impens Francis F Matondo Mariette M Cossart Pascale P Hamon Mélanie A MA

Cell reports 20180401 4

Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translatio ...[more]

PMID: 29694890

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Infection Reveals a Modification of SIRT2 Critical for Chromatin Association.

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Infection Reveals a Modification of SIRT2 Critical for Chromatin Association.

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