Nuclear addressing provides a clue for the transforming activity of amino-truncated CCN3 proteins.

Abstract

CCN3 is a founding member of the CCN (Cyr61, Ctgf, Nov) family of cell growth and differentiation regulators. These secreted proteins are key regulators in embryonic development, and are associated with severe pathologies including fibrotic diseases and cancers. CCN3 was discovered as a MAV integration site in an avian nephroblastoma. Previous work established that the amino-truncated protein expressed in this tumor was inducing morphological transformation of chicken embryo fibroblasts, whereas the full-length secreted CCN3 protein was inhibiting cell growth. Amino-truncated variants were identified in cancer cell lines. Since the lack of signal peptide was expected to alter the fate of the truncated proteins, we hypothesized that modifications of CCN3 subcellular addressing could be responsible for the oncogenic activities of CCN3. The CCN proteins are composed of four structural modules (IGFBP, TSP1, VWC, and CT). We report that amino-truncated variants of CCN3 are addressed to the nucleus and that the carboxyterminal (CT) module of CCN3 is responsible for the nuclear addressing. Furthermore, our data identify nuclear CCN3 variants as potential transcriptional regulators. In this context, the CT module confers on nuclear CCN3 proteins a negative regulatory effect on transcription. We propose that the nuclear localization of amino-truncated CCN3 proteins be correlated to oncogenicity.

• Authors: Nathalie Planque, Chang Long Li, Simon Saule, Anne-Marie Bleau, Bernard Perbal
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 99 Issue 1 Pg. 105-16 (Sep 01 2006) ISSN: 0730-2312 [Print] United States
• PMID: 16598765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immediate-Early Proteins
• Intercellular Signaling Peptides and Proteins
• Nuclear Localization Signals
• Recombinant Proteins
• Repressor Proteins
• Connective Tissue Growth Factor
• Green Fluorescent Proteins

Topics

• Animals
• Base Sequence
• Cell Line
• Cell Nucleus (metabolism)
• Connective Tissue Growth Factor
• Cricetinae
• Green Fluorescent Proteins (genetics, metabolism)
• Immediate-Early Proteins (genetics, metabolism)
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Molecular Sequence Data
• Nuclear Localization Signals (genetics)
• Recombinant Proteins (genetics, metabolism)
• Repressor Proteins (genetics, metabolism)
• Sequence Deletion
• Transcription, Genetic