NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

Hilary A. Feister, Kitti Torrungruang, Pasutha Thunyakitpisal, Gretchen E. Parker, Simon J. Rhodes, Joseph P. Bidwell

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The mechanisms underlying the coupling of type I collagen and matrix metalloproteinase (MMP) expression to cell structure and adhesion are poorly understood. We propose that nuclear matrix architectural transcription factors link cell structure and transcription via their association with nuclear matrix subdomains and by their capacity for altering promoter geometry. NP/NMP4 are nuclear matrix proteins that contain from five to eight Cys2His2 zinc fingers. Some NP/NMP4 isoforms bind to the rat type collagen α1 (I) polypeptide chain promoter in the manner of architectural transcription factors and alter basal transcription in osteoblast-like cells (Thunyakitpisal et al. in review). Certain isoforms of NP/NMP4 are identical to CIZ, Cas-interacting zinc finger protein, a nucleocytoplasmic shuttling protein that associates with focal adhesions and regulates MMP expression [Nakamoto et al. (2000): Mol Cell Biol 20:1649-1658]. To better understand the role of subnuclear architecture in collagen and MMP expression, we mapped the osteoblast nuclear distribution of NP/NMP4 proteins and identified the functional motifs necessary for nuclear localization and nuclear matrix targeting. Immunofluorescence microscopy was used to determine the cellular and subnuclear distribution of native NP/NMP4 proteins and green fluorescent protein (GFP)-NP/NMP4 fusion proteins in osteoblast-like cells. All GFP-NP/NMP4 fusion proteins localized to the nucleus, but accumulated in distinct nuclear matrix subdomains. The zinc finger domain was necessary and sufficient for nuclear import and matrix targeting. We conclude that the arrangement of the NP/NMP4 zinc fingers largely determines the subnuclear location of these isoforms. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)506-517
Number of pages12
JournalJournal of Cellular Biochemistry
Volume79
Issue number3
DOIs
StatePublished - Sep 7 2000

Keywords

  • Architectural transcription factors
  • Bone
  • CIZ
  • Matrix metalloproteinases
  • Zinc fingers collagen

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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