Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells

作者：Ukekawa Ryo; Miki Kensuke; Fujii Michihiko; Hirano Hisashi; Ayusawa Dai^*

来源：Genes to Cells, 2007, 12(3): 397-406.

DOI：10.1111/j.1365-2443.2007.01057.x

5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells.

• 出版日期2007-3