Ectopic overexpression of Drosophila lamin C is stage-specific lethal.
To gain insight into the function of the developmentally regulated A-type lamins we transformed Drosophila melanogaster with a construct containing the hsp70 promoter followed by the Drosophila lamin C (an analog of vertebrate A-type lamins) cDNA. Lamin C was expressed ectopically after heat shock of embryos and localized to the nucleus. No phenotypic change was observed after lamin C expression in embryos that normally do not contain lamin C. However, ectopic expression of lamin C during most larval (but not pupal) stages stalled growth, inhibited ecdysteroid signaling (in particular during the larval-prepupal transition), resulted in development of melanotic tumors, and finally caused death. During pupation in control animals, when massive apoptosis of larval tissues takes place, lamin C is proteolyzed into a fragment with a size similar to that predicted by caspase cleavage. The ectopically expressed lamin C is identically cleaved, resulting in a large increase of the steady-state level of the lamin C fragment. A null mutation of the dcp-1 gene, one of the two known Drosophila caspase genes, also results in development of melanotic tumors and larval death, suggesting that the ectopically expressed lamin C inhibits apoptosis through competitive inhibition of caspase activity.
Stuurman
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N
Maurice E. Müller Institut am Biozentrum, Universität Basel, Klingelbergstrasse 70, Basel, CH-4055, Switzerland. stuurman@rubim.leidenuniv.nl
Delbecque
J P
JP
Callaerts
P
P
Aebi
U
U
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D061945:Caspase Inhibitors; D004331:Drosophila melanogaster / Q000254:growth & development*; D005804:Genes, Lethal; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D018869:Heat-Shock Response; D034904:Lamin Type A; D034882:Lamins; D007814:Larva / Q000254:growth & development; D008543:Melanins; D009369:Neoplasms; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics*
D061945:Caspase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D034904:Lamin Type A; D034882:Lamins; D008543:Melanins; D009687:Nuclear Proteins; C440308:lamin C