CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment normal and malignant hematopoiesis

摘要

CCN2 protein structure. Schematic representation of the full length CCN2 protein, which is made up by a signal peptide and 4 protein domains, depicted by the blue cylinders. Domain 1 consists of the insulin-like growth factor binding protein (IGFBP) module and domain 2 contains the von Willebrand factor C (VWC) module, together forming the N-terminal fragment of the protein. Domain 3 consists of the thrombospondin type 1 repeat (TSP1) module and domain 4 contains the C-terminal cysteine knot (CT) module, together forming the C-terminal fragment of the protein. The N- and C-terminal fragments are joint by a hinge region. Between the different domains, multiple cleavage sites are present, were CCN2 is cleaved by proteases, plasmin, chymotrypsin and matrix metalloproteinases. Loss of the signal peptide leads to intracellular retention of the protein. The protein contains 2 glycosylation sites. The functional relevance of glycosylation is, however, still unknown. Other (not depicted) posttranscriptional and posttranslational modifications to which the protein is subject to, are splicing, regulation by miRNAs and multimerisation