The CCN Family of Proteins: A Critical Approach to the Multi-Modular Structure of the CCN Domains

The CCN family of proteins is composed of six members (CCN1-CCN6) sharing a tetra-modular organization and a striking conservation of their primary structure. The CCN acronym was originally assigned in 1993 by P. Bork to three newly discovered factors (originally called CTGF, CYR61, and NOV), which he proposed to constitute a new family of proteins on the basis of their common physical features. Six years later, three other proteins (Wisp1-3), sharing the same tetramodular organization, joined the family (figure 1). The HUGO-recognized acronyms for the CCN proteins were officialized in 2018[1]. The CCN family turned out to contain positive and negative regulators of cell proliferation and differentiation, with pro- and anti-tumorigenic activities. A significant amount of work has been performed to identify the participation of the constitutive modules in these biological features. The aim of this review is to briefly examine the potential roles assigned to the constitutive modules of CCN proteins and propose a critical view of the structural basis for their interactions and functions.