| Yazarlar |
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 |
| 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 |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | CANCER RESEARCH |
| Dergi ISSN | 0008-5472 |
| Dergi Tarandığı Indeksler | SCI |
| Makale Dili | İngilizce |
| Basım Tarihi | 07-2016 |
| Cilt No | 76 |
| Sayı | 13 |
| Sayfalar | 3802 / 3812 |
| Doi Numarası | 10.1158/0008-5472.CAN-15-2498 |
| Makale Linki | http://cancerres.aacrjournals.org/cgi/doi/10.1158/0008-5472.CAN-15-2498 |
| Atıf Sayıları | |
| WoS | 95 |
