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Exploring the role of REDD1 in mTOR activation
Author(s) -
McGhee Nora K.,
Jefferson Leonard S.,
Kimball Scot R.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.312.6
Subject(s) - pi3k/akt/mtor pathway , p70 s6 kinase 1 , endocrinology , medicine , insulin , phosphorylation , leucine , protein kinase b , mtorc1 , chemistry , messenger rna , biology , microbiology and biotechnology , signal transduction , amino acid , biochemistry , gene
REDD1 is a protein of unknown function that has previously been shown to be important for repression of mTOR activity in response to DNA damage, hypoxia, glucose deprivation, and glucocorticoid treatment. We hypothesized that REDD1 expression would increase during fasting and rapidly fall after refeeding, thereby mediating mTOR signaling to mRNA translation via phosphorylation of its substrates S6K1 and 4E‐BP1. To test these hypotheses in vivo male Sprague‐Dawley rats were fasted overnight and were allowed to re‐feed for 45 min. In gastrocnemius muscle REDD1 protein and mRNA increase with fasting and fall with re‐feeding. To further examine the mechanism involved in regulation of REDD1 expression, Rat2 fibroblasts were starved of serum and leucine for 2 h then leucine or insulin was added back for 30 min. In these experiments the amount of REDD1 protein increases with starvation and decreases upon insulin, but not leucine, add‐back. The siRNA knock‐down of REDD1 in Rat2 cells enhances S6K1 and 4E‐BP1 phosphorylation that occur with insulin add‐back. These results are consistent with a role for REDD1 in inhibition of mTOR activity under low insulin conditions. Supported by grants DK13499 and DK15658