Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression.
We previously showed that targeting of protein phosphatase 1 (PP1) to the nuclear envelope (NE) by the A-kinase anchoring protein, AKAP149, correlates with nuclear assembly of B-type lamins in vitro. We demonstrate here that failure of AKAP149-mediated assembly of B-type lamins into the nuclear lamina at the end of mitosis is followed by apoptosis, and induces expression of the gene encoding A-type lamins in cells that normally do not express lamins A/C. In HeLa cells, inhibition of PP1 association with the NE mediated by a peptide containing the PP1-binding domain of AKAP149 results in failure of B-type lamins to assemble, and in their rapid caspase-dependent proteolysis. However, assembly of lamins A/C is not affected. Nonetheless, apoptosis follows within hours of nuclear reformation after mitosis. In lymphoid KE37 cells, which do not express lamins A/C, inhibition of B-type lamin assembly triggers rapid synthesis and nuclear assembly of both lamins A and C before apoptosis takes place. The results indicate that nuclear assembly of B-type lamins is essential for cell survival. They also suggest that mistargeting of B-type lamins at the end of mitosis elicits a tentative rescue process to assemble a nuclear lamina in lymphoid cells that normally do not express lamins A/C.
Steen
R L
RL
Institute of Medical Biochemistry, University of Oslo, 0317 Oslo, Norway.
Collas
P
P
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells; D006801:Humans; D034882:Lamins; D008214:Lymphocytes / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054645:Protein Phosphatase 1; D021381:Protein Transport
D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D034882:Lamins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D015739:Nocodazole