Yamaki Y, Kagawa H, Hatta T, Natsume T, Kawahara H

The Sonic hedgehog (Shh) signaling pathway plays a crucial role in cell proliferation and differentiation via Patched1 (Ptc1), a 12-pass transmembrane receptor protein. The C-terminal cytoplasmic tail of Ptc1 can be cleaved to release the 7th intracellular domain (ICD7), whose function is still unclear. In this study, we found that ...

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the ICD7 fragment of Ptc1 associates with polyubiquitinated species. Using mass spectrometry, we identified a cluster of E3 ubiquitin ligase complex as novel Ptc1 ICD7-binding proteins. In particular, Ptc1 ICD7 interacted with most components of the Cullin-2 (CUL2)-based E3 ligase complex, including TCEB1 (EloC), TCEB2 (EloB), ZYG11B, and CUL2 itself. To address the significance of CUL2-based E3 ligase in Ptc1 function, we examined the effects of CUL2 knockdown on Shh-induced osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Indeed, knockdown of CUL2 abolished the Shh-induced stem cell differentiation. These results suggest that CUL2-based E3 ligase complex may play a role in Shh- and Ptc1-dependent signaling pathways.

Date: Mar. 01, 2016

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