Critical roles for SoxC transcription factors in development and cancer

Abstract

Sox4, Sox11 and Sox12 constitute the group C of Sry-related HMG box proteins. They are co-expressed in embryonic neuronal progenitors and in mesenchymal cells in many developing organs. More closely related to each other than to any other proteins, they nevertheless bind DNA and activate transcription in vitro with different efficiencies. Sox4-null embryos and Sox11-null newborns die from heart malformations and the latter display widespread defects, while Sox12-null mice are viable and do not show obvious malformations. Sox4 facilitates differentiation of lymphocytes, pancreatic beta cells, osteoblasts and acts in redundancy with Sox11 to promote neuronal differentiation. Sox4 and Sox11 are upregulated in many tumor types in humans, where their roles in cell survival, proliferation, and metastasis remain controversial. Together, these data hint that Sox4 and Sox11 regulate cell differentiation, proliferation and survival in multiple essential processes, and suggest that they may act in redundancy to control many more developmental, physiological and pathological processes than currently known.

Fig. 1

Conserved structural features of human SoxC proteins. HMG, high-mobility-group box DNA-binding domain; TAD, transactivation domain. Amino acid positions at the beginning and ending of each domain are shown.

Fig. 2

Widespread, overlapping expression of SoxC genes during embryonic development. In situ hybridization analysis of SoxC gene expression in 11.5-day-old mouse embryos. Signal from hybridized RNA is shown in red. Cell nuclei are counterstained with DAPI. f, forebrain; m, midbrain; s, spinal cord; c, craniofacial mesenchyme; v, vertebrae primordia; h, heart; li, liver; g, gut; t, genital tubercle. Reproduced with permission from Dy et al. (2008).