作者
Taro Hitosugi, Jun Fan, Tae-Wook Chung, Katherine Lythgoe, Xu Wang, Jianxin Xie, Qingyuan Ge, Ting-Lei Gu, Roberto D Polakiewicz, Johannes L Roesel, Georgia Z Chen, Titus J Boggon, Sagar Lonial, Haian Fu, Fadlo R Khuri, Sumin Kang, Jing Chen
发表日期
2011/12/23
期刊
Molecular cell
卷号
44
期号
6
页码范围
864-877
出版商
Elsevier
简介
Many tumor cells rely on aerobic glycolysis instead of oxidative phosphorylation for their continued proliferation and survival. Myc and HIF-1 are believed to promote such a metabolic switch by, in part, upregulating gene expression of pyruvate dehydrogenase (PDH) kinase 1 (PDHK1), which phosphorylates and inactivates mitochondrial PDH and consequently pyruvate dehydrogenase complex (PDC). Here we report that tyrosine phosphorylation enhances PDHK1 kinase activity by promoting ATP and PDC binding. Functional PDC can form in mitochondria outside of the matrix in some cancer cells and PDHK1 is commonly tyrosine phosphorylated in human cancers by diverse oncogenic tyrosine kinases localized to different mitochondrial compartments. Expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leads to decreased cell proliferation under hypoxia and increased …
学术搜索中的文章
T Hitosugi, J Fan, TW Chung, K Lythgoe, X Wang, J Xie… - Molecular cell, 2011