STARD3: A Lipid Transfer Protein in Breast Cancer and Cholesterol Trafficking

International audienceSTARD3 was isolated in the early 1990s in a study aimed at finding new genes implicated in breast cancer. The function of the STARD3 gene, referred to at that time as Metastatic Lymph Node clone number 64 (MLN64), remained a mystery until the discovery of the steroidogenic acute regulatory protein (StAR/STARD1). Indeed, homology searches showed a region of significant similarity between StAR and the carboxy-terminal half of STARD3. This homology proved to be functionally relevant with both proteins being cholesterol carriers; however, quite early it appeared that they were very distinct in terms of expression, subcellular localization, and function. It was then reported that STARD3 was part of a family of 15 human proteins that shared a conserved StAR-related lipid transfer (START) domain. Structurally, the STARD3 protein distinguishes itself by the presence of an additional conserved domain spanning the amino-terminal half of the protein that we named the MLN64-N-terminal (MENTAL) domain. This domain contains most of the functional properties that have been attributed to STARD3. This chapter will present our current understanding of STARD3 function in cancer, cell biology, and cholesterol trafficking