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A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B.

1994; Springer Nature; Volume: 13; Issue: 22 Linguagem: Inglês

10.1002/j.1460-2075.1994.tb06878.x

1460-2075

E. Britta-Mareen Traenckner, S. Wilk, Patrick A. Baeuerle,

interferon and immune responses

Research Article15 November 1994free access A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B. E.B. Traenckner E.B. Traenckner Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author S. Wilk S. Wilk Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author P.A. Baeuerle P.A. Baeuerle Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author E.B. Traenckner E.B. Traenckner Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author S. Wilk S. Wilk Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author P.A. Baeuerle P.A. Baeuerle Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. Search for more papers by this author Author Information E.B. Traenckner1, S. Wilk1 and P.A. Baeuerle1 1Institute of Biochemistry, Albert-Ludwigs-University, Freiburg, Germany. The EMBO Journal (1994)13:5433-5441https://doi.org/10.1002/j.1460-2075.1994.tb06878.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Activation of the inducible transcription factor NF-kappa B involves removal of the inhibitory subunit I kappa B-alpha from a latent cytoplasmic complex. It has been reported that I kappa B-alpha is subject to both phosphorylation and proteolysis in the process of NF-kappa B activation. In this study, we present evidence that the multicatalytic cytosolic protease (proteasome) is involved in the degradation of I kappa B-alpha. Micromolar amounts of the peptide Cbz-Ile-Glu(O-t-Bu)-Ala-leucinal (PSI), a specific inhibitor of the chymotrypsin-like activity of the proteasome, prevented activation of NF-kappa B in response to tumor necrosis factor-alpha (TNF) and okadaic acid (OA) through inhibition of I kappa B-alpha degradation. The m-calpain inhibitor Cbz-Leu-leucinal was ineffective. In the presence of PSI, a newly phosphorylated form of I kappa B-alpha accumulated in TNF- and OA-stimulated cells. However, the covalent modification of I kappa B-alpha was not sufficient for activation of NF-kappa B: no substantial NF-kappa B DNA binding activity appeared in cells because the newly phosphorylated form of I kappa B-alpha was still tightly bound to p65 NF-kappa B. Pyrrolidinedithiocarbamate, an antioxidant inhibitor of NF-kappa B activation which did not interfere with proteasome activities, prevented de novo phosphorylation of I kappa B-alpha as well as its subsequent degradation. This suggests that phosphorylation of I kappa B-alpha is equally necessary for the activation of NF-kappa B.(ABSTRACT TRUNCATED AT 250 WORDS) Previous ArticleNext Article Volume 13Issue 221 November 1994In this issue RelatedDetailsLoading ...