Beclin 1 self-association is independent of autophagy induction by amino acid deprivation and rapamycin treatment

2010 ◽  
Vol 110 (5) ◽  
pp. 1262-1271 ◽  
Author(s):  
Shelly Adi-Harel ◽  
Shlomit Erlich ◽  
Eran Schmukler ◽  
Sarit Cohen-Kedar ◽  
Oshik Segev ◽  
...  
Keyword(s):  
Amino Acid ◽  
Beclin 1 ◽  
Amino Acid Deprivation ◽  
Rapamycin Treatment ◽  
Autophagy Induction ◽  
Self Association

scholarly journals The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation

2002 ◽  
Vol 22 (15) ◽  
pp. 5575-5584 ◽  
Author(s):  
Tao Peng ◽  
Todd R. Golub ◽  
David M. Sabatini
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Transcriptional Profiling ◽  
Mammalian Target Of Rapamycin ◽  
Glucose Deprivation ◽  
Amino Acid Deprivation ◽  
Nucleotide Synthesis ◽  
Rapamycin Treatment ◽  
B Lymphoma Cells ◽  
Nutrient Use

ABSTRACT RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.

scholarly journals The VMP1-Beclin 1 interaction regulates autophagy induction

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Maria I. Molejon ◽  
Alejandro Ropolo ◽  
Andrea Lo Re ◽  
Veronica Boggio ◽  
Maria I. Vaccaro
Keyword(s):  
Beclin 1 ◽  
Autophagy Induction

scholarly journals Amino acid regulation of gene transcription of rat insulin-like growth factor-binding protein-1

2000 ◽  
Vol 164 (3) ◽  
pp. R11-R16 ◽  
Author(s):  
A Takenaka ◽  
K Komori ◽  
T Morishita ◽  
SI Takahashi ◽  
T Hidaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Gene Transcription ◽  
Binding Protein ◽  
Present Observation ◽  
Insulin Like Growth Factor ◽  
Amino Acid Deprivation ◽  
Cis Acting ◽  
Factor Binding ◽  
Responsive Element

To investigate the molecular mechanisms of increased transcription of the insulin-like growth factor-binding protein-1 (IGFBP-1) gene in dietary protein-deprived animals, the cis-acting sequence that is involved in this regulation was analyzed. We first showed that IGFBP-1 gene transcription was up-regulated by amino acid deprivation in cultured liver cell lines: H4IIE and HuH-7. Since HuH-7 cells showed a greater increase in IGFBP-1 mRNA in response to amino acid deprivation, this cell line was used in further experiments. Using a promoter function assay, we found that up-regulation of promoter activity responding to amino acid deprivation was abolished by deleting the region between -112 and -81 bp from the cap site from the gene construct. This cis-acting region includes the insulin-responsive element (IRE) and glucocorticoid responsive element (GRE) of IGFBP-1. In summary, the present observation suggests that the 32-bp (-112 to -81) in the IGFBP-1 gene 5' promoter region is involved in the induction of the IGFBP-1 gene in response to amino acid deprivation.

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