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 previo usly named as Orpheus was identical to Oct-1, a member of the POU doma in family. Oct-1 represses the collagenase gene, one of the cellular a ging-associated genes, by interacting with an AT-rich cis-element in t he 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 cel lular aging process, however, this subspecies of Oct-1 disappeared fro m 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 a mount of nuclear Oct-1 protein were reduced in the aging process and r esumed after immortalization. However, the whole cellular amounts of O ct-1 protein were not significantly changed during either process. Thu s, 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 repres sive apparatus by anchoring nuclear matrix attachment regions onto the nuclear lamina in the nuclear periphery.