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Am J Clin Exp Immunol 2012;1(1):56-66
Review Article
Regulation and function of nuclear IκBα in inflammation and cancer
Ivana Vancurova, Ales Vancura
Department of Biological Sciences, St. John’s University, New York, NY 11439, USA.
Received April 27, 2012; accepted May 16, 2012; Epub May 22, 2012; Published June 30, 2012
Abstract: The nuclear translocation and accumulation of IΚBα represents an important mechanism regulating
transcription of NFΚB-dependent pro-inflammatory and anti-apoptotic genes. The nuclear accumulation of IΚBα can be
induced by post-induction repression in stimulated cells, inhibition of the CRM1-dependent nuclear IΚBα export by
leptomycin B, and by the inhibition of the 26S proteasome. In addition, IΚBα is constitutively localized in the nucleus of
human neutrophils, likely contributing to the high rate of spontaneous apoptosis in these cells. In the nucleus, IΚBα
suppresses transcription of NFΚB-dependent pro-inflammatory and anti-apoptotic genes, representing an attractive
therapeutic target. However, the inhibition of NFΚB-dependent genes by nuclear IΚBα is promoter specific, and depends
on the subunit composition of NFΚB dimers and post-translational modifications of the recruited NFΚB proteins. In
addition, several recent studies have demonstrated an NFΚB-independent role of the nuclear IΚBα. In this review, we
discuss the mechanisms leading to the nuclear accumulation of IΚBα and its nuclear functions as potential targets for
anti-inflammatory and anti-cancer therapies. (AJCEI1204003).
Keywords: IΚBα, NFΚB, nuclear protein transport, gene transcription
Address all correspondence to:
Dr. Ivana Vancurova
Department of Biology
St. John's University, 8000 Utopia Parkway
Queens, NY 11439, USA.
Tel: 718 990-6409
E-mail: vancuroi@stjohns.edu
Review Article
Regulation and function of nuclear IκBα in inflammation and cancer
Ivana Vancurova, Ales Vancura
Department of Biological Sciences, St. John’s University, New York, NY 11439, USA.
Received April 27, 2012; accepted May 16, 2012; Epub May 22, 2012; Published June 30, 2012
Abstract: The nuclear translocation and accumulation of IΚBα represents an important mechanism regulating
transcription of NFΚB-dependent pro-inflammatory and anti-apoptotic genes. The nuclear accumulation of IΚBα can be
induced by post-induction repression in stimulated cells, inhibition of the CRM1-dependent nuclear IΚBα export by
leptomycin B, and by the inhibition of the 26S proteasome. In addition, IΚBα is constitutively localized in the nucleus of
human neutrophils, likely contributing to the high rate of spontaneous apoptosis in these cells. In the nucleus, IΚBα
suppresses transcription of NFΚB-dependent pro-inflammatory and anti-apoptotic genes, representing an attractive
therapeutic target. However, the inhibition of NFΚB-dependent genes by nuclear IΚBα is promoter specific, and depends
on the subunit composition of NFΚB dimers and post-translational modifications of the recruited NFΚB proteins. In
addition, several recent studies have demonstrated an NFΚB-independent role of the nuclear IΚBα. In this review, we
discuss the mechanisms leading to the nuclear accumulation of IΚBα and its nuclear functions as potential targets for
anti-inflammatory and anti-cancer therapies. (AJCEI1204003).
Keywords: IΚBα, NFΚB, nuclear protein transport, gene transcription
Address all correspondence to:
Dr. Ivana Vancurova
Department of Biology
St. John's University, 8000 Utopia Parkway
Queens, NY 11439, USA.
Tel: 718 990-6409
E-mail: vancuroi@stjohns.edu
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