The mouse RACK1 gene is regulated by nuclear factor-κB and contributes to cell survival

Receptor for activated C kinase 1 (RACK1) is a multifunctional, WD motif-containing protein important in regulating several cell surface receptors and intracellular protein kinases. To better understand its function, we cloned the mouse RACK1 gene and found it contains eight exons and seven introns, and maps to mouse chromosome 11B1.2-1.3. Promoter analysis identified NF-kappaB as an important transcription factor for promoter activity. In PC-12 cells, nerve growth factor (NGF), which activates nuclear factor-kappaB (NF-kappaB), maintained RACK1 levels and promoted cell survival in serum-free medium. Inhibitors of NF-kappaB activation blocked NGF-stimulated survival and RACK1 expression, whereas transgenic expression of RACK1 promoted survival in cells deprived of serum and NGF. Thus, RACK1 gene expression is induced by NF-kappaB and RACK1 contributes to NF-kappaB-mediated cell survival.