Unknown,Transcriptomics,Genomics,Proteomics

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BxPC-3 cells: growth in different nutrients


ABSTRACT: The MondoA transcription factor forms a heterocomplex with its obligate partner Mlx to regulate ~75% of glucose-dependent transcription. By mediating glucose-induced activation of thioredoxin-interacting protein (TXNIP), MondoA directly represses glucose uptake. Given the predominant role of MondoA in controlling glucose-dependent transcription and glucose uptake, we asked whether glutamine regulates MondoA activity. Expression profiles from glucose and glutamine starved BxPC-3 cells (-G-Q) were compared with those from cells grown in glucose only (+G-Q), glutamine only (-G+Q) or glucose plus glutamine (+G+Q). As expected, TXNIP expression was highly induced by glucose. However, the addition of glutamine repressed the glucose-dependent induction of TXNIP. We show that glutamine inhibits MondoA-dependent transcriptional activation of TXNIP by triggering the recruitment of a histone deacetylase-dependent corepressor to the amino terminus of MondoA. Consistent with the repression of TXNIP, glucose uptake is elevated in cells grown in the presence of glucose and glutamine. Finally, alpha-ketoglutarate, a tricarboxylic acid cycle intermediate, also blocks MondoA-dependent activation of TXNIP and stimulates glucose uptake. Together, these results suggest that glutamine-dependent mitochondrial anapleurosis stimulates glucose uptake by restricting TXNIP expression via MondoA:Mlx complexes. Four growth conditons; four biological replicates

ORGANISM(S): Homo sapiens

SUBMITTER: Don Ayer 

PROVIDER: E-GEOD-17632 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity.

Kaadige Mohan R MR   Looper Ryan E RE   Kamalanaadhan Sadhaasivam S   Ayer Donald E DE  

Proceedings of the National Academy of Sciences of the United States of America 20090817 35


Glucose and glutamine are abundant nutrients required for cell growth, yet how cells sense and adapt to changes in their levels is not well understood. The MondoA transcription factor forms a heterocomplex with its obligate partner Mlx to regulate approximately 75% of glucose-dependent transcription. By mediating glucose-induced activation of thioredoxin-interacting protein (TXNIP), MondoA:Mlx complexes directly repress glucose uptake. We show here that glutamine inhibits transcriptional activat  ...[more]

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