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Status |
Public on Aug 17, 2009 |
Title |
BxPC-3 cells: growth in different nutrients |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
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.
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Overall design |
Four growth conditons; four biological replicates
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Contributor(s) |
Ayer D, Kaadige M |
Citation(s) |
19706488 |
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Submission date |
Aug 13, 2009 |
Last update date |
Feb 22, 2018 |
Contact name |
Mohan Rao Kaadige |
E-mail(s) |
mohan.kaadige@hci.utah.edu
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Phone |
801-585-5169
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Fax |
801-585-6410
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Organization name |
Huntsman Cancer Institute
|
Department |
Oncological Sciences
|
Lab |
Don Ayer
|
Street address |
2000 Circle of Hope
|
City |
Salt Lake City |
State/province |
UT |
ZIP/Postal code |
84112 |
Country |
USA |
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Platforms (1) |
GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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Samples (12)
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GSM440127 |
control vs. glucose alone_rep 4 |
GSM440128 |
control vs. glucose plus glutamine_rep 1 |
GSM440129 |
control vs. glucose plus glutamine_rep 2 |
GSM440130 |
control vs. glucose plus glutamine_rep 3 |
GSM440131 |
control vs. glucose plus glutamine_rep 4 |
GSM440132 |
control vs. glutamine alone_rep 1 |
GSM440133 |
control vs. glutamine alone_rep 2 |
GSM440134 |
control vs. glutamine alone_rep 3 |
GSM440135 |
control vs. glutamine alone_rep 4 |
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Relations |
BioProject |
PRJNA118625 |