A cell cycle regulatory network controlling NF - j B subunit activity and function
نویسندگان
چکیده
Aberrantly active NF-jB complexes can contribute to tumorigenesis by regulating genes that promote the growth and survival of cancer cells. We have investigated NF-jB during the cell cycle and find that its ability to regulate the G1-phase expression of key proto-oncogenes is subject to regulation by the integrated activity of IjB kinase (IKK)a, IKKb, Akt and Chk1. The coordinated binding of NF-jB subunits to the Cyclin D1, c-Myc and Skp2 promoters is dynamic with distinct changes in promoter occupancy and RelA(p65) phosphorylation occurring through G1, S and G2 phases, concomitant with a switch from coactivator to corepressor recruitment. Akt activity is required for IKK-dependent phosphorylation of NF-jB subunits in G1 and G2 phases, where Chk1 is inactive. However, in S-phase, Akt is inactivated, while Chk1 phosphorylates RelA and associates with IKKa, inhibiting the processing of the p100 (NF-jB2) subunit, which also plays a critical role in the regulation of these genes. These data reveal a complex regulatory network integrating NF-jB with the DNA-replication checkpoint and the expression of critical regulators of cell proliferation. The EMBO Journal (2007) 26, 4841–4855. doi:10.1038/ sj.emboj.7601899; Published online 25 October 2007 Subject Categories: chromatin & transcription; cell cycle
منابع مشابه
Retraction: 'A cell cycle regulatory network controlling NF-κB subunit activity and function'.
The above article from The EMBO Journal, published online on 25 October 2007, has been retracted by agreement between the authors, the journal Chief Editor and Head of Scientific Publications, EMBO, Bernd Pulverer. The authors’ statement follows below. We have recently become aware that there are a number of issues with figures included in our 2007 research article entitled ‘A cell cycle regula...
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