Author
Hyun-Seok Kim
Other affiliations: University of Minnesota, Yonsei University, Johns Hopkins University ...read more
Bio: Hyun-Seok Kim is an academic researcher from Baylor College of Medicine. The author has contributed to research in topics: Medicine & Hepatocellular carcinoma. The author has an hindex of 38, co-authored 141 publications receiving 7284 citations. Previous affiliations of Hyun-Seok Kim include University of Minnesota & Yonsei University.
Topics: Medicine, Hepatocellular carcinoma, KSTAR, SIRT3, Tokamak
Papers published on a yearly basis
Papers
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TL;DR: It is shown that Sirt3 functions in vivo to regulate and maintain basal ATP levels and as a regulator of mitochondrial electron transport and implicate protein acetylation as an important regulator of Complex I activity.
Abstract: Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport. We note that Sirt3−/− mouse embryonic fibroblasts have a reduction in basal ATP levels. Reconstitution with wild-type but not a deacetylase-deficient form of Sirt3 restored ATP levels in these cells. Furthermore in wild-type mice, the resting level of ATP correlates with organ-specific Sirt3 protein expression. Remarkably, in mice lacking Sirt3, basal levels of ATP in the heart, kidney, and liver were reduced >50%. We further demonstrate that mitochondrial protein acetylation is markedly elevated in Sirt3−/− tissues. In addition, in the absence of Sirt3, multiple components of Complex I of the electron transport chain demonstrate increased acetylation. Sirt3 can also physically interact with at least one of the known subunits of Complex I, the 39-kDa protein NDUFA9. Functional studies demonstrate that mitochondria from Sirt3−/− animals display a selective inhibition of Complex I activity. Furthermore, incubation of exogenous Sirt3 with mitochondria can augment Complex I activity. These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels.
1,145 citations
TL;DR: It is demonstrated that Sirt1(+/-) mice develop tumors in multiple tissues, whereas activation of SIRT1 by resveratrol treatment reduces tumorigenesis, and it is shown that many human cancers exhibit reduced levels ofSIRT1 compared to normal controls.
754 citations
TL;DR: These results identify SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor and human breast and other human cancer specimens exhibit reduced Sirt3 levels.
733 citations
TL;DR: It is demonstrated that SIRT2 regulates the anaphase-promoting complex/cyclosome activity through deacetylation of its coactivators, APC(CDH1) and CDC20, and is a tumor suppressor through its role in regulating mitosis and genome integrity.
457 citations
TL;DR: It is shown that SIRT1 forms a complex with FOXO3a and NRF1 on the SIRT6 promoter and positively regulates expression of SIRT 6, which negatively regulates glycolysis, triglyceride synthesis, and fat metabolism by deacetylating histone Lysine 9 in the promoter of many genes involved in these processes.
429 citations
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TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.
9,980 citations
TL;DR: According to the analysis, old men plus gastric fundus or antrum of CFB were strongly suggested to perform ESD if precancerous lesions were found and young women with low-grade intraepithelial neoplasia could select regular follow-up.
3,491 citations
TL;DR: A full understanding of the redox control of apoptotic initiation and execution could underpin the development of therapeutic interventions targeted at oxidative stress-associated disorders.
2,834 citations
01 Jan 2013
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
2,616 citations
TL;DR: The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them.
Abstract: Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.
2,136 citations