Dissociation of oct-1 from the nuclear peripheral structure induces the cellular aging-associated collagenase gene expression

Shin Ichiro Imai, Seiji Nishibayashi, Koji Takao, Masayuki Tomifuji, Tadahiro Fujino, Mayumi Hasegawa, Toshiya Takano

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2407-2419
Number of pages13
JournalMolecular biology of the cell
Volume8
Issue number12
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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