Review
All purpose Sox: The many roles of Sox proteins in gene expression

https://doi.org/10.1016/j.biocel.2009.07.006Get rights and content

Abstract

Sox proteins are found in all metazoans and are active in many developmental processes. Their function as transcription factors is governed by their DNA-binding properties as much as by their interactions with other transcription factors and cofactors, and subject to modulation by posttranslational modifications. Although most Sox proteins predominantly function as transcriptional activators, there is also evidence for transcriptional repression and architectural roles. Further effects involve complex formation of Sox proteins with transcriptionally relevant factors off DNA. Sox proteins may be additionally active on the posttranscriptional level and are therefore remarkably versatile regulators of gene expression.

Introduction

Transcription factors of the Sox protein family regulate many different developmental processes and also control homeostasis in adult tissues. With only 20 Sox genes in the mammalian genome (Schepers et al., 2002), one and the same Sox protein must participate in many developmental processes. Available evidence furthermore suggests that the functions of a particular Sox protein in different developmental processes are usually not identical. It follows that Sox protein function must be adaptable to developmental situations and cellular contexts.

Numerous situations have been reported in which two or more Sox proteins are simultaneously expressed. In some cases, they perform redundant or synergistic functions, in others they are antagonistic or responsible for different aspects of the developmental process. This review will focus on the mechanisms by which the transcriptional activity of Sox proteins can be adapted to different tasks, but also on the properties of Sox proteins that may be responsible for intrinsic functional differences. For a general overview on Sox proteins and a discussion of their transcriptional activities in evolutionary terms or in the context of specific developmental processes, the reader is referred to other reviews in the recent literature (Lefebvre et al., 2007, Guth and Wegner, 2008, Wegner and Stolt, 2005) as well as in this issue.

Section snippets

Functional diversity among Sox proteins

Sox proteins are divided in groups. Whereas the SoxB1, SoxB2, SoxC, SoxD, SoxE and SoxF groups are found in all bilaterians, others only exist in some species (Bowles et al., 2000, Wegner, 1999). The SoxA group, for instance, is specific for mammals. It consists of Sry which was the first member of the Sox family to be identified (see review by R. Lovell-Badge in this issue). Sox proteins of the same group usually have greater than 80% sequence identity in their DNA-binding HMG-domain and share

Alternate roles of Sox proteins

Although Sox proteins have a strong direct influence on transcription, there is increasing evidence for additional indirect mechanisms. As already mentioned, SoxB1 proteins are not only believed to exert their influence in stem cells of the central nervous system by activating pluripotency and proliferation genes. They also form complexes and thereby inactivate proneural proteins that would otherwise drive the cells into neuronal differentiation (Graham et al., 2003, Bylund et al., 2003). Part

Future directions

Although much has been learnt in recent years on Sox protein function in development down to the molecular level, there are still several areas of uncharted territory. In upcoming years, it needs to be better defined how Sox proteins obtain specificity in their action, especially under conditions where two distantly related Sox proteins are co-expressed in the same cell, but obviously perform different functions. In this context it will be helpful to have a closer look at binding specificities

Acknowledgements

Work in the author's laboratory is supported by grants from IZKF Erlangen, Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie.

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