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Sci. STKE, 20 March 2001
Vol. 2001, Issue 74, p. tw5
[DOI: 10.1126/stke.2001.74.tw5]


Transcription An I{kappa}B Sink

The transcription factor NF-{kappa}B has critical functions in control of immune and inflammatory responses (see STKE Review by Rothwarf and Karin). The required strict control of NF-{kappa}B transcriptional activity is mediated in part by inhibitory I{kappa}B proteins. When the I{kappa}B proteins are degraded, NF-{kappa}B activity is increased. I{kappa}B proteins appear to act in multiple ways to hold NF-{kappa}B activity in check. When it interacts with NF-{kappa}B, I{kappa}Bα appears to hide the nuclear localization sequence of the NF-{kappa}B Rel subunit and also to inhibit DNA binding by NF-{kappa}B. I{kappa}Bα also moves between the cytoplasm and nucleus through the actions of a nuclear localization sequence and a nuclear export sequence that interacts with the importin protein CRM1. Such nuclear export may also carry NF-{kappa}B-I{kappa}B complexes out of the nucleus and contribute to transcriptional control. Tam and Sen now report that the regulatory properties appear to differ in various I{kappa}B family members. In particular, they show that I{kappa}Bβ and I{kappa}B{epsilon} do not shuttle out of the nucleus by CRM1-dependent transport. The authors suggest that, rather than facilitating nuclear export of NF-{kappa}B, I{kappa}Bβ and I{kappa}B{epsilon} function primarily by sequestration of NF-{kappa}B in the cytoplasm.

W. F. Tam, R. Sen, I{kappa}B family members function by different mechanisms. J. Biol. Chem. 276, 7701-7704 (2001). [Abstract] [Full Text]

Citation: An I{kappa}B Sink. Sci. STKE 2001, tw5 (2001).

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