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The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling.

The NOVH protein belongs to the emerging CCN [Connective tissue growth factor (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth regulators sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Two members of the family (CYR61 and CTGF) are positive regulators of cell proliferation, whereas NOVH and two other members (ELM1 and RCOP-1) exhibit features of negative regulators of growth. The multimodular structure of these proteins suggests that their biological role(s) may depend on interactions with several factors as well as proteins constitutive of the extracellular matrix. To gain insight into the functionality of these domains, we have used a two-hybrid system to identify proteins interacting with NOVH. We report here that the C-terminal domain confers on the full-length NOVH protein the capacity to bind fibulin 1C, a protein of the extracellular matrix that interacts with several other regulators of cell adhesion. Furthermore, we show that a natural N-truncated isoform of NOVH produced by cells expressing the full-length NOVH protein also binds fibulin 1C with a high affinity, and we hypothesize that the production of truncated isoforms of NOVH (and probably of other CCN proteins) may be a critical aspect in the modulation of their biological activity. These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions.

Pubmed ID: 9927660 RIS Download

Mesh terms: Animals | Calcium-Binding Proteins | Carrier Proteins | Cell Adhesion | Cell Line | Cloning, Molecular | Connective Tissue Growth Factor | Dogs | Extracellular Matrix Proteins | Gene Library | Glutathione Transferase | Growth Inhibitors | Growth Substances | HeLa Cells | Humans | Immediate-Early Proteins | Intercellular Signaling Peptides and Proteins | Nephroblastoma Overexpressed Protein | Recombinant Fusion Proteins | Recombinant Proteins | Signal Transduction | Spodoptera | Transfection

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA071933
  • Agency: NCI NIH HHS, Id: CA71933

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