求助一篇文献PNAS

饶冠华

1: Proc Natl Acad Sci U S A. 2009 Aug 17. [Epub ahead of print] Links
# o2 M6 i% @" c+ e. ~Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity.Kaadige MR, Looper RE, Kamalanaadhan S, Ayer DE.' R. M2 Z6 k3 T9 B( Q6 t# A$ l
Huntsman Cancer Institute, Department of Oncological Sciences and Department of Chemistry, University of Utah, 2000 Circle of Hope, Room 4365, Salt Lake City, UT 84112-5550.' F& I; P) J2 o7 f8 q* K

( Y, N9 C  p9 a4 `. EGlucose 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 activation of TXNIP by triggering the recruitment of a histone deacetylase-dependent corepressor to the amino terminus of MondoA. Therefore, in the presence of both glucose and glutamine, TXNIP expression is low, which favors glucose uptake and aerobic glycolysis; the Warburg effect. Consistent with MondoA functioning upstream of TXNIP, MondoA knockdown reduces TXNIP expression, elevates glucose uptake and stimulates cell proliferation. Although glutamine has many intracellular fates, a cell permeable analog of a tricarboxylic acid cycle (TCA) intermediate, alpha-ketoglutarate, also blocks the transcriptional activity of MondoA at the TXNIP promoter and stimulates glucose uptake. Together our data suggest that glutamine-dependent mitochondrial anapleurosis dictates glucose uptake and aerobic glycolysis by blocking MondoA:Mlx-dependent transcriptional activation of TXNIP. We propose that this previously unappreciated coordination between glutamine and glucose utilization defines a metabolic checkpoint that restricts cell growth when subthreshold levels of these essential nutrients are available.
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链接：http://www.ncbi.nlm.nih.gov/site ... criptional+activity

njrmcljf

见附件。

franklinhg

谢谢了  很好的 学习不倦