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Accumulation of multiple forms of lamin A with down‐regulation of FACE‐1 suppresses growth in senescent human cells
Author(s) -
Ukekawa Ryo,
Miki Kensuke,
Fujii Michihiko,
Hirano Hisashi,
Ayusawa Dai
Publication year - 2007
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01057.x
Subject(s) - lamin , biology , nuclear lamina , hela , senescence , microbiology and biotechnology , cell cycle , bromodeoxyuridine , cell growth , cell type , cell , nuclear protein , nucleus , genetics , gene , transcription factor
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.