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An IκB Sink

Science's STKE  20 Mar 2001:
Vol. 2001, Issue 74, pp. tw5
DOI: 10.1126/stke.2001.74.tw5

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

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