Transcriptional and posttranscriptional regulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase during liver regeneration.

Rosa, José Luís; Tauler, Albert; Lange, Alex J.; Pilkis, S J; Bartrons, Ramón

doi:10.1073/pnas.89.9.3746

Cited by 17 publications

(20 citation statements)

References 46 publications

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“…Transcription of the c-fos gene was only induced by 2.0-fold at 30 min (Fig. 2B, compare first two lanes) which is in agreement with the fact that regulation of expression of the c-fos gene in the regenerating liver is post-transcriptional (43). A darker exposure of the autoradiogram presented in Fig.…”

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingsupporting

confidence: 71%

“…Expression of the genes involved in gluconeogenesis, PEPCK, and TAT also increases following partial hepatectomy (Fig. 1A) in order for the liver to maintain glucose homeostasis and compensate for the loss of mass (41)(42)(43). The level of the PEPCK mRNA, as expected, increased in 30 min and remained at the induced level until 6 h following hepatectomy (41)(42)(43).…”

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 69%

“…1A) in order for the liver to maintain glucose homeostasis and compensate for the loss of mass (41)(42)(43). The level of the PEPCK mRNA, as expected, increased in 30 min and remained at the induced level until 6 h following hepatectomy (41)(42)(43). The induction of the PEPCK mRNA is probably due to transcriptional regulation of the PEPCK gene (through glucocorticoids and glucagon) and post-transcriptional stabilization of the mRNA by glucocorticoids (44).…”

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 93%

“…The induction of the PEPCK mRNA is probably due to transcriptional regulation of the PEPCK gene (through glucocorticoids and glucagon) and post-transcriptional stabilization of the mRNA by glucocorticoids (44). Comparison of the time course of induction of the mRNA levels for cat-1 and c-jun indicates that cat-1 is a delayed early response gene, whereas c-jun is an immediate early response gene (41)(42)(43). The induction of expression of the cat-1 gene in the regenerating liver involves two mRNA transcripts (7.9 and 3.4 kb), as is shown in poly(A) ϩ RNA from the regenerating liver (Fig.…”

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 99%

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Molecular Sites of Regulation of Expression of the Rat Cationic Amino Acid Transporter Gene

Aulak

Liu

et al. 1996

Journal of Biological Chemistry

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Cat-1 is a protein with a dual function, a high affinity, low capacity cationic amino acid transporter of the y ؉ system and the receptor for the ecotropic retrovirus. We have suggested that Cat-1 is required in the regenerating liver for the transport of cationic amino acids and polyamines in the late G 1 phase, a process that is essential for liver cells to enter mitosis. In our earlier studies we had shown that the cat-1 gene is silent in the quiescent liver but is induced in response to hormones, insulin, and glucocorticoids, and partial hepatectomy. Here we demonstrate that cat-1 is a classic delayed early growth response gene in the regenerating liver, since induction of its expression is sensitive to cycloheximide, indicating that protein synthesis is required. The peak of accumulation of the cat-1 mRNA (9-fold) by 3 h was not associated with increased transcriptional activity of the cat-1 gene in the regenerating liver, indicating posttranscriptional regulation of expression of this gene. Induction of the cat-1 gene results in the accumulation of two mRNA species (7.9 and 3.4 kilobase pairs (kb)). Both mRNAs hybridize with the previously described rat cat-1/2.9-kb cDNA clone. However, the 3 end of a longer rat cat-1 cDNA (rat cat-1/6.5-kb) hybridizes only to the 7.9-kb mRNA transcript. Sequence analysis of this clone indicated that the two mRNA species result from the use of alternative polyadenylation signals. The 6.5-kb clone contains a number of AT-rich mRNA destabilizing sequences which is reflected in the half-life of the cat-1 mRNAs (90 min for 7.9-kb mRNA and 250 min for 3.4-kb mRNA). Treatment of rats with cycloheximide superinduces the level of the 7.9-kb cat-1 mRNA in the kidney, spleen, and brain, but not in the liver, suggesting that cell type-specific labile factors are involved in its regulation. We conclude that the need for protein synthesis for induction of the cat-1 mRNA, the short lived nature of the mRNAs, and the multiple sites for regulation of gene expression indicate a tight control of expression of the cat-1 gene within the regenerating liver and suggest that y ؉ cationic amino acid transport in liver cells is regulated at the molecular level.

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Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingsupporting

confidence: 71%

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 69%

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 93%

Section: Cat-1 Is a Delayed Early Response Gene In The Regeneratingmentioning

confidence: 99%

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Molecular Sites of Regulation of Expression of the Rat Cationic Amino Acid Transporter Gene

Aulak

Liu

et al. 1996

Journal of Biological Chemistry

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“…Studies have shown that there is an acute fall in insulin and an increase in glucagon levels immediately after hepatectomy both of which begin to renormalize within a few hours, thereby preventing the hypoglycemia which might accompany the loss of liver mass (4,5). Previously, we and others (6)(7)(8)(9) showed that phosphoenol pyruvate kinase (PEPCK)' and other genes involved in glucose homeostasis are rapidly up-or downregulated in the regenerating liver, thus allowing the remnant liver to maintain glucose balance.…”

Section: Introductionmentioning

confidence: 99%

High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.

Haber¹,

Chin²,

Chuang³

et al. 1995

J. Clin. Invest.

137

116

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The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6-phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states. (J. Clin. Invest. 1995. 95:832-841.)

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Calmodulin Expression During Rat Liver Regeneration

et al. 1994

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We have investigated the messenger RNAs expressed from the three calmodulin genes during rat liver regeneration. The results revealed that all the calmodulin transcripts increased from 8 hr after a partial hepatectomy, although differences in the timing and the level of expression from the three genes were observed. Calmodulin I transcripts peaked at 16 hr, whereas calmodulin II and calmodulin III progressively increased from 8 to 24 hr. At 24 hr after surgery, calmodulin I, calmodulin II and the 2.3 kb calmodulin III transcripts reached values of a 6-fold increase, whereas the 0.8 kb product of calmodulin III increased 25-fold. At 30 hr the levels of all the calmodulin transcripts were similar to those observed at 24 hr. The transcription rates of the three calmodulin genes augmented after hepatectomy (calmodulin I and calmodulin II twofold and calmodulin III fourfold), indicating that the elevation of the calmodulin transcripts could be, at least partially, the result of this increase in the transcription rates. The total calmodulin concentration also increased twofold at 24 hr after hepatectomy. We also report that the administration of the beta-adrenergic blocker, D,L-propranolol inhibited the accumulation of calmodulin protein without significantly affecting the increase of the messenger RNAs. These results indicate that the expression of calmodulin observed during liver regeneration could be regulated by cyclic AMP at the translational or posttranslational level.

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Transcriptional and posttranscriptional regulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase during liver regeneration.

Cited by 17 publications

References 46 publications

Molecular Sites of Regulation of Expression of the Rat Cationic Amino Acid Transporter Gene

Molecular Sites of Regulation of Expression of the Rat Cationic Amino Acid Transporter Gene

High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.

Calmodulin Expression During Rat Liver Regeneration

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