Adenosine-containing molecules amplify glucose signaling and enhance txnip expression.
Eukaryotic cells sense extracellular glucose concentrations via diverse mechanisms to regulate the expression of genes involved in metabolic control. One such example is the tight correlation between the expression of thioredoxin-interacting protein (Txnip) and extracellular glucose levels. In this report, we show that the transcription of the Txnip gene is induced by adenosine-containing molecules, of which an intact adenosine moiety is necessary and sufficient. Txnip promoter contains a carbohydrate response element, which mediates the induction of Txnip expression by these molecules in a glucose-dependent manner. Max-like protein X and MondoA are transcription factors previously shown to stimulate glucose-dependent Txnip expression and are shown here to convey stimulatory signals from extracellular adenosine-containing molecules to the Txnip promoter. The regulatory role of these molecules may be exerted via amplifying glucose signaling. Hence, this revelation may pave the way for interventions aimed toward metabolic disorders resulting from abnormal glucose homeostasis.
Yu
Fa-Xing
FX
Institute of Molecular and Cell Biology, Proteos, Singapore.
Goh
Shuang-Ru
SR
Dai
Ru-Ping
RP
Luo
Yan
Y
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002352:Carrier Proteins; C403128:MLX protein, human; C485496:MLXIP protein, human; D012333:RNA, Messenger; C486715:TXNIP protein, human; D009243:NAD; D013879:Thioredoxins; D000255:Adenosine Triphosphate; D005947:Glucose; D000241:Adenosine