Skip to main content
Article thumbnail
Location of Repository

Novel IκBα Proteolytic Pathway in WEHI231 Immature B Cells

By Shigeki Miyamoto, Bradley J. Seufzer and Stuart D. Shumway

Abstract

The Rel/NF-κB family of transcription factors is sequestered in the cytoplasm of most mammalian cells by inhibitor proteins belonging to the IκB family. Degradation of IκB by a phosphorylation-dependent ubiquitin-proteasome (inducible) pathway is believed to allow nuclear transport of active Rel/NF-κB dimers. Rel/NF-κB (a p50–c-Rel dimer) is constitutively nuclear in murine B cells, such as WEHI231 cells. In these cells, p50, c-Rel, and IκBα are synthesized at high levels but only IκBα is rapidly degraded. We have examined the mechanism of IκBα degradation and its relation to constitutive p50–c-Rel activation. We demonstrate that all IκBα is found complexed with c-Rel protein in the cytoplasm. Additionally, rapid IκBα proteolysis is independent of but coexistent with the inducible pathway and can be inhibited by calcium chelators and some calpain inhibitors. Conditions that prevent degradation of IκBα also inhibit nuclear p50–c-Rel activity. Furthermore, the half-life of nuclear c-Rel is much shorter than that of the cytoplasmic form, underscoring the necessity for its continuous nuclear transport to maintain constitutive p50–c-Rel activity. We observed that IκBβ, another NF-κB inhibitor, is also complexed with c-Rel but slowly degraded by a proteasome-dependent process in WEHI231 cells. In addition, IκBβ is basally phosphorylated and cytoplasmic. We thus suggest that calcium-dependent IκBα proteolysis maintains nuclear transport of a p50–c-Rel heterodimer which in turn activates the synthesis of IκBα, p50, and c-Rel to sustain this dynamic process in WEHI231 B cells

Topics: Transcriptional Regulation
Publisher: American Society for Microbiology
Year: 1998
OAI identifier: oai:pubmedcentral.nih.gov:121444
Provided by: PubMed Central
Sorry, our data provider has not provided any external links therefore we are unable to provide a link to the full text.

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.