Molecular and Cellular Biology, July 2001, p. 4837-4846, Vol. 21, No. 14
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.14.4837-4846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
B
Provides a Mechanism for Nuclear NF-
B in B Lymphocytes
andRosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454
Received 20 December 2000/Returned for modification 18 February 2001/Accepted 9 April 2001
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-
B based on the observed
properties of Rel homo- and heterodimers and I
B
. 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 I
B
, leading to a greater
propensity of heterodimers to be nuclear. We propose that subunit
composition of B-cell NF-
B reflects the inefficient retrieval of
p50-c-Rel heterodimers from the nucleus. Cell specificity may be a
consequence of c-Rel-I
B
complexes being present only in mature B
cells, which leads to nuclear c-Rel due to I
B
turnover and
shuttling of the complex.
Present address: Massachusetts General Hospital Cancer Center and
Harvard Medical School, Charlestown, MA 02129.
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