AKAP149 is a novel PP1 specifier required to maintain nuclear envelope integrity in G1 phase.
Reassembly of the nuclear envelope (NE) at the end of mitosis requires targeting of the B-type lamin protein phosphatase, PP1, to the envelope by A-kinase anchoring protein AKAP149. We show here that NE-associated AKAP149 is a novel PP1-specifying subunit involved in maintaining nuclear architecture through G1 phase. PP1 remains associated with NE-bound AKAP149 during G1 but is released from AKAP149 upon S phase entry, as AKAP149 becomes serine-phosphorylated. NE-associated AKAP149 inhibits PP1 activity towards glycogen phosphorylase but enhances PP1 phosphatase activity towards B-type lamins, indicating that AKAP149 is a B-type lamin specifying subunit of PP1. In vivo dissociation of PP1 from NE-bound AKAP149 in G1-phase nuclei triggers phosphorylation and depolymerization of A- and B-type lamins. The lamins solubilize intranuclearly without affecting the inner nuclear membrane or pore complex distribution. This correlates with the induction of a G1 arrest and, ultimately, apoptosis. We propose that AKAP149-regulated PP1 activity at the NE during G1 is required to maintain nuclear integrity and cell survival.
Steen
Rikke L
RL
Institute of Medical Biochemistry, University of Oslo, PO Box 1112 Blindern, 0317 Oslo, Norway.
Beullens
Monique
M
Landsverk
Helga B
HB
Bollen
Mathieu
M
Collas
Philippe
P
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D016193:G1 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D012995:Solubility; D013379:Substrate Specificity
D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D034921:Lamin Type B; D008565:Membrane Proteins; D004247:DNA; D010749:Phosphoprotein Phosphatases