Journal article

Structural basis for nuclear import selectivity of pioneer transcription factor SOX2.

Bikshapathi Jagga, Megan Edwards, Miriam Pagin, Kylie M Wagstaff, David Aragão, Noelia Roman, Jeffrey D Nanson, Shane R Raidal, Nicole Dominado, Murray Stewart, David A Jans, Gary R Hime, Silvia K Nicolis, Christopher F Basler, Jade K Forwood

Nature Communications | Published : 2021

Abstract

SOX (SRY-related HMG-box) transcription factors perform critical functions in development and cell differentiation. These roles depend on precise nuclear trafficking, with mutations in the nuclear targeting regions causing developmental diseases and a range of cancers. SOX protein nuclear localization is proposed to be mediated by two nuclear localization signals (NLSs) positioned within the extremities of the DNA-binding HMG-box domain and, although mutations within either cause disease, the mechanistic basis has remained unclear. Unexpectedly, we find here that these two distantly positioned NLSs of SOX2 contribute to a contiguous interface spanning 9 of the 10 ARM domains on the nuclear i..

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University of Melbourne Researchers