AMINO ACID DEPRIVATION-INDUCED EXPRESSION OF ASPARAGINE SYNTHETASE REGULATES THE GROWTH AND SURVIVAL OF CULTURED SILKWORM CELLS

2013 ◽  
Vol 83 (2) ◽  
pp. 57-68 ◽  
Author(s):  
Zhiqing Li ◽  
Li Zhu ◽  
Jian Xu ◽  
Hiroaki Mon ◽  
Jae Man Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Asparagine Synthetase ◽  
Amino Acid Deprivation ◽  
Induced Expression ◽  
Growth And Survival

scholarly journals Induction of calreticulin expression in response to amino acid deprivation in Chinese hamster ovary cells

1998 ◽  
Vol 329 (2) ◽  
pp. 389-394 ◽  
Author(s):  
Richard HEAL ◽  
John McGIVAN
Keyword(s):  
Amino Acid ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Fold Increase ◽  
Asparagine Synthetase ◽  
Mrna Levels ◽  
Amino Acid Deprivation ◽  
Ovary Cells ◽  
Protein Levels

The role of calreticulin as a stress-induced molecular chaperone protein of the endoplasmic reticulum is becoming more apparent. We characterize here the induction of calreticulin in response to complete amino acid deprivation in Chinese hamster ovary cells. Amino acid deprivation caused a 4-fold increase in calreticulin protein levels over a period of 4-10 h. In addition to an overall increase in protein levels, the glycosylation of calreticulin was increased. This glycosylation event was blocked by tunicamycin and was not required for the increase in calreticulin protein levels. Immunofluorescence studies localized calreticulin to the ER of CHO cells, and no significant change was observed after amino acid deprivation. Northern-blot analysis showed that calreticulin mRNA levels were increased approx. 10-fold in response to complete amino acid deprivation. The response was sensitive to actinomycin D and α-amanitin, implying that regulation is primarily at the level of transcription. These results are similar to the large increases in asparagine synthetase mRNA observed in response to amino acid deprivation, but the amino acid-deprivation-response element identified to be involved in asparagine synthetase induction is absent from the calreticulin promoter.

Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP

2005 ◽  
Vol 386 (9) ◽  
Author(s):  
Jude Al Sarraj ◽  
Charles Vinson ◽  
Gerald Thiel
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Gene Transcription ◽  
Leucine Zipper ◽  
Nutrient Sensing ◽  
Asparagine Synthetase ◽  
Nutrient Deprivation ◽  
Amino Acid Deprivation ◽  
Response Unit ◽  
Basic Region

AbstractAsparagine synthetase catalyses the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. In human hepatoma cells cultured in mediumcontaining amino acids, the mRNA of asparagine synthetase is not detectable by RNase protection mapping. However, maintaining the cells in amino acid-free Krebs-Ringer bicarbonate buffer strongly upregulated asparagine synthetase biosynthesis. The effect of amino acid deprivation on asparagine synthetase gene transcription is mediated by a genetic element termed the nutrient-sensing response unit. Previous studies revealed that the basic region leucine zipper (bZIP) transcription factor CREB2/ATF4 is involved in the nutrient deprivation-induced upregulation of asparagine synthetase gene transcription. Here we show that overexpression of the bZIP protein ATF5, a transcriptional activator, stimulates asparagine synthetase promoter/reporter gene transcription via the nutrient-sensing response unit. In contrast, ATF5 does not transactivate cAMP response element (CRE)-containing reporter genes. Overexpression of the C/EBP homologous transcription factor CHOP impaired transcriptional activation of the asparagine synthetase promoter following amino acid deprivation or over-expression of ATF5 or CREB2/ATF4. These data indicate that CHOP functions as a shut-off-device for nutrient deprivation-induced gene transcription.

scholarly journals The Mechanism for Transcriptional Activation of the Human ATA2 Transporter Gene by Amino Acid Deprivation is Different than That for Asparagine Synthetase

2002 ◽  
Vol 132 (10) ◽  
pp. 3023-3029 ◽  
Author(s):  
Perry J. Bain ◽  
Rene LeBlanc-Chaffin ◽  
Hong Chen ◽  
Stela S. Palii ◽  
Kelly M. Leach ◽  
...  
Keyword(s):  
Amino Acid ◽  
Transcriptional Activation ◽  
Asparagine Synthetase ◽  
Amino Acid Deprivation ◽  
Transporter Gene

Amino acid control of asparagine synthetase: relation to asparaginase resistance in human leukemia cells

1997 ◽  
Vol 272 (5) ◽  
pp. C1691-C1699 ◽  
Author(s):  
R. G. Hutson ◽  
T. Kitoh ◽  
D. A. Moraga Amador ◽  
S. Cosic ◽  
S. M. Schuster ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Enzymatic Activity ◽  
Protein Content ◽  
Culture Medium ◽  
Asparagine Synthetase ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Amino Acid Deprivation ◽  
Human Leukemia Cells

Complete amino acid deprivation in mammalian cells causes a significant enhancement in gene expression for a number of important cellular activities; among these is asparagine synthetase (AS). The data presented demonstrate that, in both nonleukemic (rat Fao hepatoma cells) and human leukemia cells (MOLT-4, NALL-1, and BALL-1), AS mRNA levels, protein content, and enzymatic activity are induced after incubation in an otherwise complete tissue culture medium that is deficient in a single amino acid or in medium that has been depleted of the amino acid asparagine by the addition of asparaginase. Complete amino acid deprivation results in a concerted increase in AS mRNA, protein, and enzymatic activity, which, in conjunction with previously published research, suggests that the mechanism of this cellular response involves transcriptional control of the AS gene. Asparaginase treatment is a standard component of acute lymphoblastic leukemia therapy for which the effectiveness is related to the inability of these cells to upregulate AS activity to a sufficient level. With regard to the asparaginase sensitivity of the three human leukemia cell lines, there was a trend toward an inverse relation to the degree of AS expression. Selection for asparaginase-resistant MOLT-4 sublines resulted in enhanced AS mRNA and protein content regardless of whether the cells had been selected by asparaginase treatment directly or asparagine was removed from the culture medium. Collectively, the data illustrate that further advances in asparaginase therapy will require additional knowledge of amino acid-dependent regulation of AS gene expression and, conversely, that asparaginase resistance represents a model system for investigating metabolite control in a clinically relevant setting.

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