TY - JOUR
T1 - Cell-specific association and shuttling of IκBα provides a mechanism for nuclear NF-κB in B lymphocytes
AU - Tam, W. F.
AU - Wang, W.
AU - Sen, R.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.21.14.4837-4846.2001
DO - 10.1128/MCB.21.14.4837-4846.2001
M3 - Article
C2 - 11416157
AN - SCOPUS:0034961236
SN - 0270-7306
VL - 21
SP - 4837
EP - 4846
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 14
ER -