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DDIT4 (DNA damage-inducible transcript 4; REDD1; RTP801) is a
stress-inducible regulatory protein activated by hypoxia, DNA damage, oxidative
stress, nutrient deprivation, glucocorticoids and other cellular stresses.
DDIT4 generally suppresses mechanistic target of rapamycin complex 1
(mTORC1) signalling, thereby reducing protein synthesis, cell
growth and anabolic metabolism while promoting stress adaptation and, in some
settings, autophagy. Increased DDIT4 can mediate anticancer effects by inhibiting
mTORC1, causing cell-cycle arrest and limiting proliferation; for example,
DDIT4 contributes to metformin-induced mTOR inhibition in prostate cancer cells.
However, tumour cells may also use DDIT4 to survive hypoxia, metabolic stress or
anticancer treatment, and DDIT4 can suppress ER-stress-induced apoptosis in some
cancer models. Loss of DDIT4 may alternatively increase mTORC1 activity and
proliferation in certain tissues.
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