Sci. STKE, 30 July 2002
Apoptosis Starved to Death
Many cells are dependent on growth factors for survival, and growth factor-independent growth is a property of many tumor cells. However, the mechanisms by which growth factors protect cells from death are not well understood. To sustain cells, growth factors maintain energy supplies by promoting expression of glucose transporters on the cell surface, an effect mediated by the protein kinase Akt (also called PKB). Edinger and Thompson now report that Akt has broader effects on access of cells to nutrients. In FL5.12 cells (murine hematopoietic pre-B cells), withdrawal of interleukin 3 causes cell death. To simplify the experimental system, the authors studied the effects of IL-3 withdrawal on nutrient transporters in cells prevented from undergoing apoptosis by expression of Bcl-xL. Withdrawal of IL-3 was associated with loss of cell surface expression of the 4F2 heavy chain (which is thought to be a chaperone that functions in amino acid transport), the low-density lipoprotein receptor (which transports cholesterol), and the transferrin receptor (which transports iron). Expression of activated Akt largely restored expression of the transporters on the cell surface in a manner that was sensitive to rapamycin, an inhibitor of the kinase mTOR. The yeast homolog of mTOR functions in adaptation of the yeast cells to changes in nutrient concentrations by controlling expression of nutrient transporters, suggesting that the mammalian protein may have retained functions similar to those of its precursor in yeast. The authors point out that rapamycin inhibits proliferation of some tumor cells, and that limitation of nutrient transport could be one mechanism by which this effect is produced.
Citation: Starved to Death. Sci. STKE 2002, tw271 (2002).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882