Boys, girls and shuttling of SRY and SOX9

Oestrogen Dependent Regulation of Gonadal Fate

“…In the presence of oestrogen SOX9 remains cytoplasmic in the early developing gonads of many nonmammalian vertebrates permitting granulosa cell development (de Santa Barbara et al 2000). However, in the absence of oestrogen, SOX9 becomes nuclear and Sertoli cell development is initiated (Sim et al 2008). Therefore, the ability of oestrogen to mediate the subcellular localization of SOX9 and directly mediate its transcription, could explain the primary mechanism by which oestrogen establishes sex in nonmammalian vertebrates.…”

“…SOX9 contains two defined nuclear localization signals (NLS) found in the C-and N-termini that are 100% conserved between mouse, human and the wallaby (Pask et al 2002). Active transport through nucleopore complex is facilitated in part by importin-, binding directly to the C-terminal NLS (Sim et al 2008). This binding is enhanced by phosphorylation of SOX9 by phosphokinase A, facilitating increased nuclear import (Malki et al 2005).…”

A role for estrogen in somatic cell fate of the mammalian gonad

“…In the presence of estrogen, SOX9 remains cytoplasmic in the early developing gonads of many nonmammalian vertebrates, permitting granulosa cell development (de Santa Barbara et al 2000). However, in the absence of estrogen, SOX9 becomes nuclear and Sertoli cell development is initiated (Sim et al 2008). Therefore, the ability of estrogen to mediate the subcellular localization of SOX9 and directly mediate its transcription, could explain the primary mechanism by which estrogen establishes sex in nonmammalian vertebrates.…”

“…SOX9 contains two defined nuclear localization signals (NLS) found in the C-and N-termini that are 100% conserved between mouse, human, and the wallaby (Pask et al 2002). Active transport through nucleopore complex is facilitated in part by importin-β, binding directly to the C-terminal NLS (Sim et al 2008). This binding is enhanced by phosphorylation of SOX9 by phosphokinase A, facilitating increased nuclear import (Malki et al 2005).…”

“…The N-terminal NLS binds calmodulin, another factor that facilitates nuclear transport of SOX9 (Argentaro et al 2003). SOX9 is also subject to SUMOylation and ubiquitination (Sim et al 2008). SUMOylation has been shown to regulate nucleocytoplasmic trafficking of several proteins while ubiquitination marks proteins for degradation.…”