The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2.
Pyruvate kinase M2 (M2-PK) controls the rate-limiting step at the end of the glycolytic pathway in normal proliferating and tumor cells. Other functions of M2-PK in addition to its role in glycolysis are little understood. The aim of this study was to identify new cellular interaction partners of M2-PK in order to discover novel links between M2-PK and cellular functions. Here we show that the SUMO-E3 ligase protein PIAS3 (inhibitor of activated STAT3) physically interacts with M2-PK and its isoenzyme M1-PK. Moreover, we demonstrate that endogenous SUMO-1-M2-PK conjugates exist in mammalian cells. Furthermore, we show that transient expression of PIAS3 but not the RING domain mutant PIAS3 (C299S, H301A) is consistent with nuclear localization of M2-PK and PIAS3 and M2-PK partially co-localize in the nucleus of these cells. This study suggests a link between PIAS3 and nuclear pyruvate kinase.
Spoden
Gilles A
GA
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria.
Morandell
Dieter
D
Ehehalt
Daniela
D
Fiedler
Marc
M
Jansen-Dürr
Pidder
P
Hermann
Martin
M
Zwerschke
Werner
W
D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases; D011770:Pyruvate Kinase