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 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.
Duband-Goulet
I
I
Département de Biologie supramoléculaire et cellulaire, Institut Jacques Monod, CNRS, Paris, France. dubandg@ijm.jussieu.fr
Courvalin
J C
JC
Buendia
B
B
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular; D002458:Cell Fractionation; D002645:Chickens; D002843:Chromatin / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D034921:Lamin Type B; D034882:Lamins; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D000097682:Lamin B Receptor
D016590:Aphidicolin; D002843:Chromatin; D003609:Dactinomycin; D004791:Enzyme Inhibitors; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor