Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis.
We have demonstrated that dynamic redistribution of nuclear-mitotic apparatus (NuMA) protein in the cell cycle is correlated temporally and spatially with its biochemical modifications. In interphase, NuMA behaves solely as a 220 kDa nuclear matrix-associated protein. After initiation of DNA condensation during mitosis, NuMA is phosphorylated by Cdc2 kinase into a 240 kDa form which is transported quickly to the centrosomal region. Once cells have passed the metaphase-anaphase transition, the 240 kDa form of NuMA either becomes a 180 kDa truncated form which is fated to be degraded completely before mitotic exit, or returns to the 220 kDa form that relocates to the daughter nuclei and remains throughout interphase. Apparently, a proteolytic enzyme is activated during the late stages of mitosis. After induction of a 180 kDa form of NuMA in interphase HeLa cells by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, nuclear apoptotic phenomena including chromatin condensation, DNA fragmentation, and micronucleation were observed. However, the same treatment did not induce apoptosis in mitotic phase-arrested HeLa cells. The 180 kDa form of NuMA was demonstrated to be a truncated product, at least lacking the tail domain. When HL60 cells were stimulated by diverse apoptosis inducers such as camptothecin, staurosporine, cycloheximide, and A23187, the extent of NuMA cleavage to produce a 180 kDa product was comparable with the degree of oligonucleosomal laddering. NuMA cleavage is likely to be a consequence of the onset of apoptosis. The intact 220 kDa NuMA functions in interphase cells to retain the nuclear structural integrity. Additionally, NuMA appears to act as a nuclear structural target for a death protease during apoptosis.
Hsu
H L
HL
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Yeh
N H
NH
D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D017209:Apoptosis / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D002467:Cell Nucleus; D004249:DNA Damage; D018604:Epitope Mapping; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D008941:Spindle Apparatus / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016203:CDC2 Protein Kinase