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Medientyp:
E-Artikel
Titel:
SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions
Beteiligte:
Bhardwaj, Abhishek;
Das, Sanjeev
Erschienen:
Proceedings of the National Academy of Sciences, 2016
Erschienen in:Proceedings of the National Academy of Sciences
Sprache:
Englisch
DOI:
10.1073/pnas.1520045113
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Significance</jats:title>
<jats:p>
SIRT6 (sirtuin 6) is a member of the highly conserved sirtuin family of NAD
<jats:sup>+</jats:sup>
-dependent deacetylases. SIRT6 regulates diverse cellular processes including tumorigenesis. However, the role of SIRT6 deacetylase activity in its tumor-suppressor functions is not well understood. Here we report that SIRT6 deacetylates nuclear PKM2 (pyruvate kinase M2). PKM2 is a glycolytic enzyme with nonmetabolic nuclear oncogenic functions. SIRT6-mediated deacetylation results in PKM2 nuclear export in an exportin 4-dependent manner. As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus SIRT6 suppresses PKM2-dependent cell proliferation and tumorigenesis. Taken together, our findings demonstrate the pivotal role of deacetylase activity in SIRT6 tumor-suppressor functions and delineate a mechanism of PKM2 nuclear export.
</jats:p>