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Published online 30 April 2001. doi:10.1083/jcb.153.3.621
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© The Rockefeller University Press, 0021-9525/2001//621 $5.00
The Journal of Cell Biology, Volume 153, Number 3, , 2001 621-626

Original Article

Mistargeting of B-Type Lamins at the End of Mitosis

: Implications on Cell Survival and Regulation of Lamins a/C Expression



Rikke L. Steena and Philippe Collasa

a Institute of Medical Biochemistry, University of Oslo, 0317 Oslo, Norway
Institute of Medical Biochemistry, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway.47-228-5149747-228-51013

philippe.collas{at}basalmed.uio.no

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.

Key Words: AKAP149 • apoptosis • lamin • mitosis • nuclear envelope

© 2001 The Rockefeller University Press

Abbreviations used in this paper: AKAP, A-kinase anchoring protein; LBR, lamin B receptor; NE, nuclear envelope; PARP, poly(ADP)ribosyl polymerase; PP1, protein phosphatase 1; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling.


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