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

Mol Biol Cell. 1997 Dec;8(12):2407-19. doi: 10.1091/mbc.8.12.2407.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cellular Senescence*
  • Collagenases / genetics
  • Collagenases / metabolism*
  • DNA / genetics
  • DNA / metabolism
  • DNA Footprinting
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / genetics*
  • Host Cell Factor C1
  • Humans
  • Lamin Type B
  • Lamins
  • Models, Biological
  • Mutation / genetics
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Octamer Transcription Factor-1
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism
  • Response Elements / genetics
  • Substrate Specificity
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics

Substances

  • DNA-Binding Proteins
  • HCFC1 protein, human
  • Host Cell Factor C1
  • Lamin Type B
  • Lamins
  • Nuclear Proteins
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Repressor Proteins
  • Transcription Factors
  • DNA
  • Collagenases