Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase.
We have previously isolated cDNA clones for several mRNAs that are dramatically increased in livers of fasted mice refed a high carbohydrate diet. We report here the sequence and regulation of one such mRNA; the 6.8-kilobase mRNA has an open reading frame of 2481 nucleotides, and the coded protein contains 827 amino acid residues (Mr of 90,000) with a 30% identity and an additional 42% similarity in an approximately 300-amino acid stretch to Escherichia coli glycerol-3-phosphate acyltransferase. The p90 mRNA is highly expressed in liver and in adipose tissue. When previously fasted mice were refed a high carbohydrate, fat-free diet, the liver mRNA level for p90 was increased about 20-fold at 8 h. Administration of dibutyryl cAMP at the time of refeeding prevented the increase in the p90 mRNA by 70%. In addition, there was no increase in the p90 mRNA level when previously starved streptozotocin-diabetic mice were refed. In diabetic animals, the p90 mRNA level increased by 2-fold 1 h after insulin injection and reached a maximum of 19-fold after 6 h. The increase in transcription rate of the p90 gene preceded that of steady state mRNA level caused by fasting/refeeding, and cAMP abolished the increase in transcription. Transcription of the p90 gene was not detectable in either fasted or refed streptozotocin-diabetic mice, but increased 4-fold 30 min after insulin administration and further increased up to 8-fold at 2 h. On-going protein synthesis was necessary for this increase.
Shin
D H
DH
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115.
Paulauskis
J D
JD
Moustaïd
N
N
Sul
H S
HS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D003001:Cloning, Molecular; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames; D011061:Poly A; D011506:Proteins / Q000235:genetics*; D012313:RNA; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013806:Theophylline / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D003994:Bucladesine; D013806:Theophylline; D005992:Glycerol-3-Phosphate O-Acyltransferase