Transcriptional regulation of mouse 6-phosphogluconate dehydrogenase by ADD1/SREBP1c.
6-Phosphogluconate dehydrogenase (6PGDH) constitutes the pentose phosphate pathway and produces NADPH. 6PGDH is also considered as a lipogenic gene since NADPH is a pivotal cofactor for lipogenesis. Thus, it is important to elucidate how 6PGDH is regulated by various signals related to energy homeostasis. Here, we provide several evidences that ADD1/SREBP1c regulates the expression of mouse 6PGDH gene. DNase I footprinting assay and point mutation studies revealed that the E-box (CANNTG) motif in the promoter of mouse 6PGDH is an important cis-regulatory element for ADD1/SREBP1c. 6PGDH mRNA is highly expressed in white adipose tissue and tightly modulated by nutritional status. Furthermore, we found that ADD1/SREBP1c mediates insulin-dependent 6PGDH expression and that PI3-kinase is an important linker for its regulation. Taken together, these data suggest that ADD1/SREBP1c is a key transcription factor for 6PGDH gene expression and would coordinate glucose metabolism and lipogenesis for energy homeostasis.
Rho
Ho Kyung
HK
Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Park
Jiyoung
J
Suh
Jung Hee
JH
Kim
Jae Bum
JB
D041721:3T3-L1 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism*; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497388:Srebf1 protein, mouse; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D010734:Phosphogluconate Dehydrogenase