Editors' ChoiceNeurobiology

CASK Goes to the Nucleus

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Science's STKE  21 Mar 2000:
Vol. 2000, Issue 24, pp. tw12
DOI: 10.1126/stke.2000.24.tw12

The major role of membrane-associated guanylate kinases (MAGUKs) such as CASK is thought to be assembling protein complexes at sites of cell-cell contact. However, Hseuh et al. now report that CASK may be a coactivator of Tbr-1, a transcription factor that is highly expressed in rat embryonic brain. The two proteins interact through the guanylate kinase-like domain of CASK and are found in a complex in both transfected cells and in embryonic rat brain cells. About 20% of CASK colocalized with Tbr-1 in nuclei during brain development. CASK also stimulated Tbr-1 activity in cultured neurons, and the authors propose that reelin may be an endogenous target gene of Tbr-1-CASK, because its 5' upstream region contains a T-element DNA sequence that is recognized by Tbr-1. Dynamic interaction of CASK with its various binding partners may regulate its subcellular distribution because the presence of CASK-binding proteins at the cell surface inhibited nuclear localization.

Hsueh, Y-P., Wang, T-F., Yang, F-C., and Sheng, M. (2000) Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404: 298-302. [Online Journal]

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