New insight into CCN3 interactions - Nuclear CCN3 : fact or fantasy?

Cellular biological processes are governed by several interconnected signaling pathways that allow fine tuning of proliferation, growth arrest, differentiation, and death. Central to this integrated control is a hierachy of regulatory circuitry that likely requires the interplay of multi-protein complexes. Multimolecular complexes are known to provide flexibility and subtle integrated responses to a variety of paracrine or autocrine signals that may be synergistic and antagonist.In the past decade, a new family of signaling proteins, known as CCN proteins, has emerged [1,2]. These secreted matricellular proteins are believed to play key roles in several fundamental biological processes, among which cell proliferation, differentiation and apoptosis have been the most studied [3]. Their involvement in osteogenesis, angiogenesis, regeneration, fibrosis and cancer development is now well documented, and we have previously proposed [1,4] that the CCN proteins might act as scaffolding or adaptor proteins that would permit the interconnection between independent signaling pathways that is required for balanced biological processes.In spite of the increasing amount of interest devoted to CCN proteins, very little is known regarding their mode of action. This is probably due to the fascinating multimodular organisation of the CCN proteins with a high cystein content and a well-known tendency to aggregate, that make it difficult to obtain large amounts of pure protein and to develop reliable reagents. Reports have flourished demonstrating detection of CCN RNAs and proteins in various organs, increased or decreased expression of CCN proteins in normal and pathological conditions, association of CCN expression with differentiation or proliferative status in given tissues, but very few have addressed key questions such as to the precise functions of CCN proteins, their mechanisms of action, and whether they are genuine signaling molecules or co-factors.Very elegant work publishe