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Vol. 8, Issue 12, 2407-2419, December 1997
Department of Microbiology, Keio University School of Medicine,
Shinjuku-ku, Tokyo-160, Japan
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.
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