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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shankar, Eswar Ramírez-bergeron, Diana L. Qu, Cheng-kui Yu, Wen-mei Ye, Fang Liu, Xia Raza, Syed Li, Qiang Hoppel, Charles L. Hakimi, Parvin Danielpour, David Hanson, Richard W. Tang, Fangqiang Yang, Yu-chung Dunwoodie, Sally L. Fujioka, Hisashi |
| Description | Author Affiliation: Li Q ( From the Departments of Biochemistry.) |
| Abstract | CREB-binding protein (CBP)/p300 interacting transactivator with glutamic acid (Glu) and aspartic acid (Asp)-tail 2 (Cited2) was recently shown to be essential for gluconeogenesis in the adult mouse. The metabolic function of Cited2 in mouse embryonic stem cells (mESCs) remains elusive. In the current study, the metabolism of glucose was investigated in mESCs, which contained a deletion in the gene for Cited2 (Cited2(Δ/-)). Compared with its parental wild type counterpart, Cited2(Δ/-) ESCs have enhanced glycolysis, alternations in mitochondria morphology, reduced glucose oxidation, and decreased ATP content. Cited2 is recruited to the hexokinase 1 (HK1) gene promoter to regulate transcription of HK1, which coordinates glucose metabolism in wild type ESCs. Reduced glucose oxidation and enhanced glycolytic activity in Cited2(Δ/-) ESCs correlates with defective differentiation during hypoxia, which is reflected in an increased expression of pluripotency marker (Oct4) and epiblast marker (Fgf5) and decreased expression of lineage specification markers (T, Gata-6, and Cdx2). Knockdown of hypoxia inducible factor-1 in Cited2(Δ/-) ESCs re-initiates the expression of differentiation markers T and Gata-6. Taken together, a deletion of Cited2 in mESCs results in abnormal mitochondrial morphology and impaired glucose metabolism, which correlates with a defective cell fate decision. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 1 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-01-03 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Embryonic Stem Cells Metabolism Glycolysis Physiology Mitochondria Repressor Proteins Trans-Activators Transcription, Genetic Adenosine Triphosphate Biosynthesis Genetics Animals Antigens, Differentiation Cell Hypoxia Cytology Glucose Hexokinase Mice Mice, Knockout Octamer Transcription Factor-3 Oxidation-Reduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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