SIRT2 Mediated Deacetylation and Tetramerization of Pyruvate Kinase Directs Glycolysis and Tumor Growth
Yazarlar (14)
Park Seong Hoon
Türkiye
Prof. Dr. Özkan ÖZDEN
Kafkas Üniversitesi, Türkiye
Guoxiang Liu
Türkiye
Ha Yong Song
Türkiye
Yueming Zhu
Türkiye
Yufan Yan
Türkiye
Xianghui Zou
Türkiye
Hong Jun Kang
Türkiye
Haiyan Jiang
Türkiye
Daniel R Principe
Türkiye
Yong Iı Cha
Türkiye
Meejeon Roh
Türkiye
Athanassios Vassilopoulos
Türkiye
David Gius
Türkiye
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | CANCER RESEARCH | ||
| Dergi ISSN | 0008-5472 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI | ||
| Makale Dili | İngilizce | Basım Tarihi | 07-2016 |
| Cilt / Sayı / Sayfa | 76 / 13 / 3802–3812 | DOI | 10.1158/0008-5472.CAN-15-2498 |
| Makale Linki | http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-15-2498 | ||
| Özet |
| Sirtuins participate in sensing nutrient availability and directing metabolic activity to match energy needs with energy production and consumption. However, the pivotal targets for sirtuins in cancer are mainly unknown. In this study, we identify the M2 isoform of pyruvate kinase (PKM2) as a critical target of the sirtuin SIRT2 implicated in cancer. PKM2 directs the synthesis of pyruvate and acetyl-CoA, the latter of which is transported to mitochondria for use in the Krebs cycle to generate ATP. Enabled by a shotgun mass spectrometry analysis founded on tissue culture models, we identified a candidate SIRT2 deacetylation target at PKM2 lysine 305 (K305). Biochemical experiments including site-directed mutants that mimicked constitutive acetylation suggested that acetylation reduced PKM2 activity by preventing tetramerization to the active enzymatic form. Notably, ectopic overexpression of a deacetylated PKM2 mutant in Sirt2-deficient mammary tumor cells altered glucose metabolism and inhibited malignant growth. Taken together, our results argued that loss of SIRT2 function in cancer cells reprograms their glycolytic metabolism via PKM2 regulation, partially explaining the tumor-permissive phenotype of mice lacking Sirt2 Cancer Res; 76(13); 3802-12. ©2016 AACR. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 120 |