Abstract
Lamins are intermediate filament proteins that constitute the main components of the lamina underlying the inner-nuclear membrane and serve to organize chromatin. Lamins (e.g., lamin-B) undergo posttranslational modifications (e.g., isoprenylation and methylation) at their C-terminal cysteine. Such modifications are thought to render optimal association of lamins with the nuclear envelop. Herein, we examined whether nuclear lamin-B undergoes carboxyl methylation in islet β cells. A 65- to 70-kDa protein was carboxyl methylated in intact rat islets and clonal β (HIT or INS) cells or in homogenates which could be immunoprecipitated using lamin-B antiserum. Incubation of purified HIT cell-nuclear fraction with [3H]S-adenosyl methionine yielded a single carboxyl methylated protein peak (ca. 65–70 kDa); this protein was immunologically identified as lamin-B. Several methylation inhibitors, including acetyl farnesyl cysteine, a competitive inhibitor of protein prenyl cysteine methylation, inhibited the carboxyl methylation of lamin-B, indicating that the carboxyl-methylated amino acid is cysteine. These findings, together with our recent observations demonstrating that inhibition of protein isoprenylation causes apoptotic death of the pancreatic β cell, raise an interesting possibility that inhibition of C-terminal cysteine modifications of lamin-B might result in disruption of nuclear assembly, leading to further propagation of apoptotic signals, including DNA fragmentation and chromatin condensation.
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More From: Biochemical and Biophysical Research Communications
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