LBR, A CHROMATIN AND LAMIN BINDING-PROTEIN FROM THE INNER NUCLEAR-MEMBRANE, IS PROTEOLYZED AT LATE STAGES OF APOPTOSIS

Chromatin condensation and apposition to the nuclear envelope is an im portant feature of the execution phase of apoptosis, During this proce ss, lamin proteins that are located between the inner nuclear membrane and heterochromatin are proteolyzed by the apoptosis-specific proteas e caspase 6. We have investigated the fate of nuclear membranes during apoptosis by studying the lamin B receptor (LBR), a transmembrane pro tein of the inner nuclear membrane. LBR interacts through its nucleopl asmic amino-terminal domain with both heterochromatin and B-type lamin s, and is phosphorylated throughout the cell cycle, but on different s ites in interphase and mitosis, The report here that: (i) the aminoter minal domain of LBR is specifically cleaved during apoptosis to genera te an similar to 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 oc curring 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.