Expressions 1985

PRODUCTION STAFFLOUISE AUSTINDANA Z. BEHRENDSENAMBER HEWITTTOSHIA SOUTHRANDY STANDLEYSHELLY WILSONhttps://openspace.dmacc.edu/expressions/1006/thumbnail.jp

Ndfip1 regulates nuclear Pten import in vivo to promote neuronal survival following cerebral ischemia

PTEN (phosphatase and tensin homologue deleted on chromosome TEN) is the major negative regulator of phosphatidylinositol 3-kinase signaling and has cell-specific functions including tumor suppression. Nuclear localization of PTEN is vital for tumor suppression; however, outside of cancer, the molecular and physiological events driving PTEN nuclear entry are unknown. In this paper, we demonstrate that cytoplasmic Pten was translocated into the nuclei of neurons after cerebral ischemia in mice. Critically, this transport event was dependent on a surge in the Nedd4 family–interacting protein 1 (Ndfip1), as neurons in Ndfip1-deficient mice failed to import Pten. Ndfip1 binds to Pten, resulting in enhanced ubiquitination by Nedd4 E3 ubiquitin ligases. In vitro, Ndfip1 overexpression increased the rate of Pten nuclear import detected by photobleaching experiments, whereas Ndfip1⁻/⁻ fibroblasts showed negligible transport rates. In vivo, Ndfip1 mutant mice suffered larger infarct sizes associated with suppressed phosphorylated Akt activation. Our findings provide the first physiological example of when and why transient shuttling of nuclear Pten occurs and how this process is critical for neuron survival.Jason Howitt, Jenny Lackovic, Ley-Hian Low, Adam Naguib, Alison Macintyre, Choo-Peng Goh, Jennifer K. Callaway, Vicki Hammond, Tim Thomas, Matthew Dixon, Ulrich Putz, John Silke, Perry Bartlett, Baoli Yang, Sharad Kumar, Lloyd C. Trotman, and Seong-Seng Ta

Rewriting desire: the construction of sexual identity in literary and legal discourse in postcolonial Ireland

The failure of the legal imaginary to reflect sexual difference in the opening decades of the postcolonial Irish state led to what in psychoanalytical terms may be described as the creation of socially abjected groups. Lesbians and gay men were numbered among such groups. The failure of official discourse to contemplate sexual difference as an integral part of Irish national identity was a residue of the Irish colonial experi- ence. The association of Ireland with the female in colonial discourse led the Irish revolutionary elite to propagate a myth of hypermasculinity. This strategy had farreaching consequences for the manner in which matters of sexual difference were to be treated in the postcolonial era. The exclusion of sexually dissident voices from official discourse did not stifle attempts at the levels of literary discourse and pressure group politics to voice alternative desires which were deemed antithetical to the heterosexual Irish state. The growth of alternative narratives of sexual identity led to a gradual transformation of the legal and cultural construction of homosexuality in Ireland. This demonstrates the power of narrative strategies to counter a dominant discourse of blindness to sexual difference and reflects a link between the cultural and legal constructions of sexual identity