Regulation of human STARD4 gene expression under endoplasmic reticulum stress.

STARD4 belongs to the STARD family of proteins that have steroidogenic acute regulatory protein-related lipid transfer domains and function in the transport and metabolism of lipids. We isolated STARD4 as a novel endoplasmic reticulum (ER) stress-responsive gene using a subtracted, ER stress-specific human cDNA library, and analyzed its transcriptional regulation under ER stress. Northern blot analysis revealed that the induction of STARD4 by ER stress was limited to the early phase. Luciferase reporter assay showed that the induction of STARD4 depended on both transcription factor ATF6 and an ERSE-like element in its promoter. To date, no other genes that are induced only during the early phase of ER stress have been identified, although the mammalian ER stress response is known to be regulated multiphasically and to induce expression of other genes. This study is a first step in elucidating the relationship between lipid metabolism and the ER stress response.