IGFBP5 is one of a family of proteins that bind to insulin-like growth factors (IGFs). It seems to regulate binding of IGFs to cell surface receptors, but there are also hints that it has IGF-independent roles. The protein is upregulated in certain tumours and, together with IGF2, it is implicated in control of muscle development. To define the roles of IGFBP5 in this process, Jennifer Pell and co-workers have examined the effects of wild-type IGFBP5 and a mutant form of the protein that cannot bind IGFs (mutIGFBP5) on differentiation of C2 myoblasts (see ). They observe that the wild-type protein inhibits myogenesis but the mutant cannot. Interestingly, however, they find that both forms of the protein inhibit apoptosis: cells expressing IGFBP5 or mutIGFBP5 exhibit higher survival rates, decreased caspase activity and reduced surface levels of annexin V. Furthermore, IGFBP5 and mutIGFBP5 protect cells from apoptosis induced by cotransfection of antisense Igf2. The authors conclude that regulation of myogenesis by IGFBP5 has two components: IGF-dependent inhibition of differentiation and IGF-independent promotion of cell survival. Given that IGFBP5 is upregulated in tumours, its IGF-independent activity could also be an important factor in cancer progression.
