Nascent polypeptide-associated complex (NAC) is an abundant cytosolic protein involved in cotranslational targeting of polypeptides to the endoplasmic reticulum (ER) membrane. NAC preparations consist of two copurifying polypeptides termed alpha- and beta-NAC that form a very stable complex in vivo and in vitro, and a functional complex can be reconstituted from the individual subunits. A dissection of the contributions of the individual subunits to NACs function revealed that both subunits are in direct contact with nascent polypeptide chains on the ribosome and that both contribute to the prevention of inappropriate interactions. Alpha-NAC is a coactivator of AP-1-mediated transcription. The alpha-NAC protein functions as a transcriptional coactivator by potentiating the activity of the chimeric Gal4-VP16 activator and of c-Jun homodimers. alpha-NAC binds to and regulates FADD function, which is a critical mediator of signal transduction pathways activated by several members of the TNF receptor gene superfamily. Human alpha-NAC is decreased in patients with Alzheimer’s disease and Down syndrome.
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