Cell-specific association and shuttling of IkappaBalpha provides a mechanism for nuclear NF-kappaB in B lymphocytes.
Cell-specific association and shuttling of IkappaBalpha provides a mechanism for nuclear NF-kappaB in B lymphocytes.
复制标题
IkappaBalpha 的细胞特异性关联和穿梭为 B 淋巴细胞中的核 NF-kappaB 提供了机制。
DOI：
10.1128/mcb.21.14.4837-4846.2001
复制
发表时间：
2001
影响因子：
5.3
通讯作者：
Sen,R
中科院分区：
文献类型：
--
作者：
Tam,WF;Wang,W;Sen,R
成熟的B淋巴细胞在细胞刺激前含有核Rel蛋白是独一无二的。这种活性主要由p50-c-rel异源二聚体组成，其对B细胞功能的重要性在几个基因改变的小鼠品系中的B细胞活性降低中得到了例证。在这里，我们根据观察到的Rel同源和异源二聚体以及IκBκBα的特性，提出了构成B细胞NF-RIB B的细胞特异性和亚基组成的机制。我们发现c-Rel缺乏核输出序列，使得从核中移除含c-Rel的络合物的效率低于移除含P65的络合物。第二，当p65和c-Rel同源二聚体与IκBα络合时，p65和c-Rel同源二聚体的核进口潜力减弱，而p50相关的异源二聚体的核进口潜力减弱，导致异二聚体更倾向于核。我们认为B细胞NF-κB的亚基组成反映了p50-c-Rel异二聚体从细胞核中的低效回收。细胞特异性可能是c-Rel-IκBα复合体只存在于成熟B细胞中的结果，这导致了IκBα周转和复合体的穿梭而导致核c-Rel。
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.