DNA Damage Inducible Transcript 3 (DDIT3)

The DDIT3 gene shows a high level of conservation in both the structural and regulatory regions to the previously described hamster gene. The human and hamster proteins share 91% amino acid identity.CHOP serves as a dominant-negative inhibitor of the transcription factors C/EBP and LAP. bacterially expressed CHOP inhibited the DNA-binding activity of C/EBP and LAP by forming heterodimers that could not bind DNA.Chop also activated Ero1-alpha (ERO1L), which encodes an ER oxidase. Consequently, the ER of stressed Chop -/- cells was hypooxidized relative to the ER of stressed wildtype cells. Pharmacologic and genetic manipulations promoting a hypooxidized ER reduced abnormal high molecular mass protein complexes and protected cells from the lethal consequences of ER stress.