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 n uclear 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 lami na at the end of mitosis is followed by apoptosis, and induces expression o f the gene encoding A-type lamins in cells that normally do not express lam ins 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 failur e of B-type lamins to assemble, and in their rapid caspase-dependent proteo lysis. However, assembly of lamins A/C is not affected. Nevertheless, apopt osis follows within hours of nuclear reformation after mitosis. In lymphoid KE37 cells, which do not express lamins AIC, inhibition of B-type lamin as sembly triggers rapid synthesis and nuclear assembly of both lamins A and C before apoptosis takes place. The results indicate that nuclear assembly o f B-type lamins is essential for cell survival. They also suggest that mist argeting 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.