Duband-Goulet I, Courvalin J C, Buendia B
Département de Biologie supramoléculaire et cellulaire, Institut Jacques Monod, CNRS, Paris, France.
J Cell Sci. 1998 May;111 ( Pt 10):1441-51. doi: 10.1242/jcs.111.10.1441.
Chromatin condensation and apposition to the nuclear envelope is an important feature of the execution phase of apoptosis. During this process, lamin proteins that are located between the inner nuclear membrane and heterochromatin are proteolyzed by the apoptosis-specific protease caspase 6. We have investigated the fate of nuclear membranes during apoptosis by studying the lamin B receptor (LBR), a transmembrane protein of the inner nuclear membrane. LBR interacts through its nucleoplasmic amino-terminal domain with both heterochromatin and B-type lamins, and is phosphorylated throughout the cell cycle, but on different sites in interphase and mitosis. We report here that: (i) the amino-terminal domain of LBR is specifically cleaved during apoptosis to generate an approximately 20 kDa soluble fragment; (ii) the cleavage of LBR is a late event of apoptosis and occurs subsequent to lamin B cleavage; (iii) the phosphorylation of LBR during apoptosis is similar to that occurring in interphase. As the association of condensed chromatin with the inner nuclear membrane persists until the late stages of apoptosis, we suggest that the chromatin binding protein LBR plays a major role in maintaining this association.
染色质凝聚并附着于核膜是细胞凋亡执行阶段的一个重要特征。在此过程中，位于内核膜与异染色质之间的核纤层蛋白会被凋亡特异性蛋白酶caspase 6进行蛋白水解。我们通过研究内核膜的跨膜蛋白核纤层B受体（LBR），来探究细胞凋亡过程中核膜的命运。LBR通过其核质氨基末端结构域与异染色质和B型核纤层蛋白相互作用，并且在整个细胞周期中都会发生磷酸化，但在间期和有丝分裂期的磷酸化位点不同。我们在此报告：（i）LBR的氨基末端结构域在细胞凋亡过程中会被特异性切割，产生一个约20 kDa的可溶性片段；（ii）LBR的切割是细胞凋亡的晚期事件，发生在核纤层B切割之后；（iii）细胞凋亡过程中LBR的磷酸化与间期发生的磷酸化相似。由于凝聚的染色质与内核膜的结合会持续到细胞凋亡的后期，我们认为染色质结合蛋白LBR在维持这种结合中起主要作用。
