Rab7 Prevents Growth Factor-Independent Survival by Inhibiting Cell-Autonomous Nutrient Transporter Expression

Growth factor withdrawal results in the endocytosis and degradation of transporter proteins for glucose and amino acids. Here, we show that this process is under the active control of the small GTPase Rab7. In the presence of growth factor, Rab7 inhibition had no effect on nutrient transporter expre...

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Bibliographic Details
Published in:Developmental cell 2003-10, Vol.5 (4), p.571-582
Main Authors: Edinger, Aimee L, Cinalli, Ryan M, Thompson, Craig B
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Adenovirus E1A Proteins - metabolism
Amino Acid Transport Systems - genetics
Amino Acid Transport Systems - metabolism
Amino Acids - pharmacology
Animals
bcl-X Protein
Blotting, Western
Carbonyl Cyanide m-Chlorophenyl Hydrazone - metabolism
Carrier Proteins - metabolism
Cell Line
Cell Survival - physiology
Chloroquine - metabolism
Dogs
Embryo, Mammalian
Fibroblasts
Flow Cytometry
Food Deprivation
Fusion Regulatory Protein 1, Heavy Chain - metabolism
Glucose - pharmacology
Glucose Transporter Type 1
Green Fluorescent Proteins
Growth Substances - physiology
Humans
Immunohistochemistry
Interleukin-3 - pharmacology
Luminescent Proteins - metabolism
Mice
Microscopy, Confocal
Monosaccharide Transport Proteins - genetics
Monosaccharide Transport Proteins - metabolism
Mutation
Precipitin Tests
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2 - metabolism
rab GTP-Binding Proteins - physiology
Time Factors
Transformation, Genetic
Tumor Suppressor Protein p53 - metabolism
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Summary:Growth factor withdrawal results in the endocytosis and degradation of transporter proteins for glucose and amino acids. Here, we show that this process is under the active control of the small GTPase Rab7. In the presence of growth factor, Rab7 inhibition had no effect on nutrient transporter expression. In growth factor-deprived cells, however, blocking Rab7 function prevented the clearance of glucose and amino acid transporter proteins from the cell surface. When Rab7 was inhibited, growth factor deprived cells maintained their mitochondrial membrane potential and displayed prolonged, growth factor-independent, nutrient-dependent cell survival. Thus, Rab7 functions as a proapoptotic protein by limiting cell-autonomous nutrient uptake. Consistent with this, dominant-negative Rab7 cooperated with E1A to promote the transformation of p53 −/− mouse embryonic fibroblasts (MEFs). These results suggest that proteins that limit nutrient transporter expression function to prevent cell-autonomous growth and survival.
ISSN:1534-5807
1878-1551
DOI:10.1016/S1534-5807(03)00291-0