Cell-specific association and shuttling of IκBα provides a mechanism for nuclear NF-κB in B lymphocytes

W. F. Tam, W. Wang, R. Sen

Research output: Contribution to journalArticlepeer-review

Abstract

Mature B lymphocytes are unique in containing nuclear Rel proteins prior to cell stimulation. This activity consists largely of p50 - c-Rel heterodimers, and its importance for B-cell function is exemplified by reduced B-cell viability in several genetically altered mouse strains. Here we suggest a mechanism for the cell specificity and the subunit composition of constitutive B-cell NF-κB based on the observed properties of Rel homo- and heterodimers and IκBα. We show that c-Rel lacks a nuclear export sequence, making the removal of c-Rel-containing complexes from the nucleus less efficient than removal of p65-containing complexes. Second, the nuclear import potential of p65 and c-Rel homodimers but not p50-associated heterodimers was attenuated when they were complexed to IκBα, leading to a greater propensity of heterodimers to be nuclear. We propose that subunit composition of B-cell NF-κB reflects the inefficient retrieval of p50 - c-Rel heterodimers from the nucleus. Cell specificity may be a consequence of c-Rel - IκBα complexes being present only in mature B cells, which leads to nuclear c-Rel due to IκBα turnover and shuttling of the complex.

Original languageEnglish (US)
Pages (from-to)4837-4846
Number of pages10
JournalMolecular and Cellular Biology
Volume21
Issue number14
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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