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.
Swiss Institute for Experimental Cancer Research, Lausanne.
M
M
Peter
J
J
Nakagawa
M
M
Dorée
J C
JC
Labbé
E A
EA
Nigg
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