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Rapid synthesis and degradation of the Regulated in Development and DNA damage (REDD1) protein in response to IGF‐I in C2C12 myotubes
Author(s) -
Frost Robert A,
Lang Charles
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.312.7
Subject(s) - mg132 , myogenesis , pi3k/akt/mtor pathway , cycloheximide , protein kinase b , protein degradation , insulin like growth factor , chemistry , biology , microbiology and biotechnology , growth factor , skeletal muscle , signal transduction , endocrinology , proteasome inhibitor , protein biosynthesis , proteasome , receptor , biochemistry
REDD1 is a stress response gene whose protein product negatively regulates signaling through the mammalian target of rapamycin (mTOR) while desensitizing the response of cells to apoptosis. Given the anabolic and protective affect of insulin‐like growth factor‐I (IGF‐I) on skeletal muscle we examined the regulation of REDD1 by IGF‐I in C2C12 myotubes. IGF‐I rapidly increased the expression of REDD1 mRNA 3‐fold. IGF‐I‐induced REDD1 expression was blocked by inhibitors of transcription and translation. IGF‐I withdrawal resulted in a rapid 70% loss of REDD1 protein within 2h. Although the loss of REDD1 was blocked by inhibition of the proteasome this was negated in the presence of cycloheximide. Consistent with this finding, MG132 increased REDD1 expression. Both IGF‐I and insulin stimulated REDD1 and they had an additive affect with dexamethasone another inducer of REDD1. IGF‐I‐stimulated REDD1 was mTOR‐dependent based on its inhibition by rapamycin. Although IGF‐I and MG132 induced REDD1 these agents had little affect on signaling downstream of mTOR. In vivo both IGF‐I and insulin stimulated REDD1 expression in the gastrocnemius. Our results suggest the REDD1 gene is positively regulated by IGF‐I and that endogenous REDD1 expression has little affect on mTOR signaling under these conditions. We speculate that increased REDD1 may function to protect muscle during stress conditions.