B Cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kB regulated c-myc transcription

Raelene J. Grumont, Andreas Strasser, Steve Gerondakis

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115 Citations (Scopus)

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 languageEnglish
Pages (from-to)1283-1294
Number of pages12
JournalMolecular Cell
Volume10
Issue number6
DOIs
Publication statusPublished - 1 Jan 2002
Externally publishedYes

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