http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2013160a.html
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Abstract
The Groucho/transducin-like Enhancer of split 1 (Gro/TLE1):Hes1
transcriptional repression complex acts in cerebral cortical neural
progenitor cells to inhibit neuronal differentiation. The molecular
mechanisms that regulate the anti-neurogenic function of the Gro/TLE1:Hes1
complex during cortical neurogenesis remain to be defined. Here we show
that prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase
NIMA-interacting 1) and homeodomain-interacting protein kinase 2 (HIPK2)
are expressed in cortical neural progenitor cells and form a complex
that interacts with the Gro/TLE1:Hes1 complex.
This association depends on the enzymatic activities of both HIPK2 and
Pin1, as well as on the association of Gro/TLE1 with Hes1, but is independent of the previously described Hes1-activated phosphorylation of Gro/TLE1. Interaction with the Pin1:HIPK2 complex results in Gro/TLE1 hyperphosphorylation and weakens both the transcriptional repression activity and the anti-neurogenic function of the Gro/TLE1:Hes1
complex.
These results provide evidence that HIPK2 and Pin1 work
together to promote cortical neurogenesis, at least in part, by
suppressing Gro/TLE1:Hes1-mediated inhibition of neuronal differentiation.
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