In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase.
The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. Phosphorylation of lamin proteins is believed to cause lamina disassembly during meiotic and mitotic M phase, but the M phase-specific lamin kinase has not been identified. Here we show that the cdc2 kinase, a major element implicated in controlling the eukaryotic cell cycle, phosphorylates chicken B-type lamins in vitro on sites that are specifically phosphorylated during M phase in vivo. Concomitantly, cdc2 kinase is capable of inducing lamina depolymerization upon incubation with isolated nuclei. One of the target sites of cdc2 kinase is identified as a motif (SPTR) conserved in the N-terminal domain of all lamin proteins. These results lead us to propose that mitotic disassembly of the nuclear lamina results from direct phosphorylation of lamins by cdc2 kinase.
Peter
M
M
Swiss Institute for Experimental Cancer Research, Lausanne.
Nakagawa
J
J
Dorée
M
M
Labbé
J C
JC
Nigg
E A
EA
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D066298:In Vitro Techniques; D007399:Interphase / Q000502:physiology; D034882:Lamins; D046911:Macromolecular Substances; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*
D034882:Lamins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase