Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.

The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, initiated by the multi-protein β-catenin destruction complex. The precise mechanisms underlying destruction complex function have remained unknown, largely because of the lack of suitable in vitro systems. Here we describe the in vitro reconstitution of an active human β-catenin destruction complex from purified components, recapitulating complex assembly, β-catenin modification, and degradation. We reveal that AXIN1 polymerization and APC promote β-catenin capture, phosphorylation, and ubiquitylation. APC facilitates β-catenin's flux through the complex by limiting ubiquitylation processivity and directly interacts with the SCFβ-TrCP E3 ligase complex in a β-TrCP-dependent manner. Oncogenic APC truncation variants, although part of the complex, are functionally impaired. Nonetheless, even the most severely truncated APC variant promotes β-catenin recruitment. These findings exemplify the power of biochemical reconstitution to interrogate the molecular mechanisms of Wnt/β-catenin signaling

Chronic Sixth Nerve Palsy

Lateral rectus paresisFour cases of petrous apex - cavernous sinus involvement by benign tumor have been seen that presented with initial clinical courses characterized by isolated lateral rectus paresis.Diagnostic studies initially performed which did not include contrast procedures were normal. Our experience with this group of patients has emphasized the localizing value of chronic isolated sixth nerve palsies.N/AAbducens nerve palsyN/AN/

Nonlinear transport and fluctuation characteristics of doped semiconductors

Fluctuation phenomena in doped n-type GaAs, at moderate applied electric fields being influenced by interelectron scattering, are interpreted in terms of effective electron temperature. Electron Fick’s diffusion coefficients in longitudinal and transfer direction are estimated

Noise and electron diffusion in doped n -type GaAs at heating electric fields

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