Impacts of a new transcription factor family: mammalian GCM proteins in health and disease

Abstract

GCM proteins constitute a small transcription factor family with a DNA-binding domain exhibiting a novel fold composed of two subdomains rigidly held together by coordination of one of two structural zinc cations. In all known cases, GCM proteins exert the role of master regulators: the prototypical family member determines gliogenesis in Drosophila melanogaster, whereas mammalian GCM proteins orchestrate divergent aspects of development and physiology in placenta, kidney, thymus, and parathyroid gland. Recent data point to an involvement of GCM proteins in different pathological contexts, such as preeclampsia, hyper- or hypoparathyroidism, and parathyroid gland tumors.

Figure 1.

Overview and domain topology of GCM proteins. Numbers to the right indicate amino acid residues in each GCM protein. To avoid superimposing multiple domains in the same GCM protein, one of the two is shown at half height. At the right, the expression site of each GCM protein is listed. Note the presence of two transactivation domains for mammalian and chick GCM proteins. For GCM2/Glide2, xeGCM, and SpGcm, the GCM domain is the only characterized domain. At the bottom, differently patterned squares corresponding to different functional domains are shown (DBD, DNA-binding domain; TA, transactivation domain; NLS, nuclear localization signal; NES, nuclear export signal; PEST, proline-glutamine-serine-threonine rich motif; ID, inhibitory domain).