Abstract
Rel/NF-κB transcription factors regulate the division and survival of B lymphocytes. Here we show that B cells lacking NF-κB1 and c-Rel fail to increase in size upon mitogenic stimulation due to a reduction in induced c-myc expression. Mitogen-induced B cell growth, although not markedly impaired by FRAP/mTOR or MEK inhibitors, required phosphatidylinositol 3-kinase (PI3K) activity. Inhibition of PI3K-dependent growth coincided with a block in the nuclear import of NF-κB1/c-Rel dimers and a failure to upregulate c-myc. In addition, PI3K was shown to be necessary for a transcription-independent increase in c-Myc protein levels that accompanies mitogenic activation. Collectively, these findings establish a role for Rel/NF-κB signaling in the mitogen-induced growth of mammalian cells, which in B lymphocytes requires a PI3K/c-myc-dependent pathway.
Original language | English |
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Pages (from-to) | 1283-1294 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 10 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Jan 2002 |
Externally published | Yes |