Dissociation of Oct-1 from the nuclear peripheral structure induces the cellular aging-associated collagenase gene expression.
The cellular aging-associated transcriptional repressor that we previously named as Orpheus was identical to Oct-1, a member of the POU domain family. Oct-1 represses the collagenase gene, one of the cellular aging-associated genes, by interacting with an AT-rich cis-element in the upstream of the gene in preimmortalized cells at earlier population-doubling levels and in immortalized cells. In these stages of cells, considerable fractions of the Oct-1 protein were prominently localized in the nuclear periphery and colocalized with lamin B. During the cellular aging process, however, this subspecies of Oct-1 disappeared from the nuclear periphery. The cells lacking the nuclear peripheral Oct-1 protein exhibited strong collagenase expression and carried typical senescent morphologies. Concomitantly, the binding activity and the amount of nuclear Oct-1 protein were reduced in the aging process and resumed after immortalization. However, the whole cellular amounts of Oct-1 protein were not significantly changed during either process. Thus, the cellular aging-associated genes including the collagenase gene seemed to be derepressed by the dissociation of Oct-1 protein from the nuclear peripheral structure. Oct-1 may form a transcriptional repressive apparatus by anchoring nuclear matrix attachment regions onto the nuclear lamina in the nuclear periphery.
Imai
S
S
Department of Microbiology, Keio University School of Medicine, Shinjuku-ku, Tokyo-160, Japan.
Nishibayashi
S
S
Takao
K
K
Tomifuji
M
M
Fujino
T
T
Hasegawa
M
M
Takano
T
T
D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D016922:Cellular Senescence; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D051863:Host Cell Factor C1; D006801:Humans; D034921:Lamin Type B; D034882:Lamins; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D050811:Octamer Transcription Factor-1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D017364:Collagenases