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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The molecular action of testis-determining factors SRY and SOX9.

Despite 10 years of work since the discovery of SRY, little is known about its biochemical function. The HMG domain, a DNA-binding and DNA-bending motif, plays a central role, being the only region conserved between species and the site of almost all clinical mutations causing XY gonadal dysgenesis. By contrast, SOX9 harbours a number of highly conserved regions, including two domains required for maximal transactivation. The beat shock protein HSP70 recognizes a specific region of SOX9 hitherto of unknown function which may facilitate the assembly of multi-protein complexes at promoter enhancer regions. The SRY and SOX9 HMG domains carry two nuclear localization signals (NLSs), one at each end which function independently and by distinct mechanisms. The N-terminal NLS is bound by calmodulin while the C-terminal NLS is bound by importin beta. Four XY gonadal dysgenesis patients with mutations in SRY NLS regions showed reduced nuclear import accompanied in some cases by reduced importin beta recognition. A campomelic dysplasia patient with SOX9 mutation outside the NLS regions also showed defective SOX9 nuclear import implying that nuclear import defects could be a common explanation for SRY and SOX9 HMG domain mutations.[1]


  1. The molecular action of testis-determining factors SRY and SOX9. Harley, V.R. Novartis Found. Symp. (2002) [Pubmed]
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