title: Boys, girls and shuttling of SRY and SOX9.
abstract: In the mammalian embryo, SRY and SOX9 are key Sertoli cell proteins that drive the development of the bipotential gonad into a testes rather than an ovary, leading ultimately to the male phenotype. Clinical SRY and SOX9 mutations causing disorders of sex development (DSD) highlight defective protein-protein interactions between SRY or SOX9, and carrier proteins required for nuclear import (importin-b and calmodulin) and nuclear export (CRM-1). The fine balance between import and export determines the levels of transcriptionally active SRY and SOX9 in the nucleus. Recently, post-translational modifications of SRY and SOX9 have been identified which affect nuclear transport. It is therefore timely that the consequences of sex-reversal mutation upon nuclear transport be reviewed. SRY and SOX9 mutations in DSD have uncovered regulatory sites for sumoylation, ubiquitination, acetylation and phosphorylation, many of which are essential for their transport and sex determining functions.
authors.affiliation: Human Molecular Genetics Laboratory, Prince Henry's Institute of Medical Research, Level 4 Block E, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, VIC 3168, Australia.
authors.forename: Helena
authors.initials: H
authors.lastname: Sim
authors.forename: Anthony
authors.initials: A
authors.lastname: Argentaro
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Harley
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein