Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cells.
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.
Ukekawa
Ryo
R
Department of Biochemistry, Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan.
Miki
Kensuke
K
Fujii
Michihiko
M
Hirano
Hisashi
H
Ayusawa
Dai
D
D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases; D045726:Metalloproteases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D017931:DNA Primers; C494847:LMNA protein, human; D034904:Lamin Type A; D008074:Lipoproteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C090764:prelamin A; D045726:Metalloproteases; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human