title: The 100-kDa proteolytic fragment of RB is retained predominantly within the nuclear compartment of apoptotic cells.
abstract: The retinoblastoma tumor suppressor protein (RB) has been shown to play a role in regulating the eukaryotic cell cycle, promoting cellular differentiation, and modulating programmed cell death. Although regulation of RB tumor suppressor activity is mediated by reversible phosphorylation, an additional posttranslational modification involves the cleavage of 42 residues from the carboxy terminus of RB during the onset of drug-induced or receptor-mediated apoptosis. We now demonstrate that a recombinant p100cl RB species localizes to the nucleus where it may retain wildtype "pocket" protein binding activity. In addition, using immunocytochemistry, we show that cleavage of the endogenous RB protein occurs in vivo in human cells and that p100cl is predominantly retained within the nuclear compartment of cells during early apoptosis. We also show that the carboxy-terminal cleavage of RB is detected immediately following caspase-3 and PARP cleavage during FAS-mediated apoptosis of MCF10 cells. These findings suggest that this cleavage event may be a component of a downstream cascade during programmed cell death.
authors.affiliation: Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Geradts
authors.forename: M M
authors.initials: MM
authors.lastname: Keane
authors.forename: S
authors.initials: S
authors.lastname: Lipkowitz
authors.forename: M
authors.initials: M
authors.lastname: Zajac-Kaye
authors.forename: F J
authors.initials: FJ
authors.lastname: Kaye
mesh_terms: D017209:Apoptosis; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein