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The Role of the Hedgehog Pathway in Chemoresistance of Gastrointestinal Cancers
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Mechanisms of Smoothened Regulation in Hedgehog Signaling

Markey Cancer Center, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40356, USA
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Author to whom correspondence should be addressed.
Academic Editors: Maria Domenica Castellone, Xiaoyan Zheng and Alexander E. Kalyuzhny
Cells 2021, 10(8), 2138; https://doi.org/10.3390/cells10082138
Received: 28 June 2021 / Revised: 5 August 2021 / Accepted: 16 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue Hedgehog Signaling in Development and Cancer 2021)
The seven-transmembrane protein, Smoothened (SMO), has shown to be critical for the hedgehog (HH) signal transduction on the cell membrane (and the cilium in vertebrates). SMO is subjected to multiple types of post-translational regulations, including phosphorylation, ubiquitination, and sumoylation, which alter SMO intracellular trafficking and cell surface accumulation. Recently, SMO is also shown to be regulated by small molecules, such as oxysterol, cholesterol, and phospholipid. The activity of SMO must be very well balanced by these different mechanisms in vivo because the malfunction of SMO will not only cause developmental defects in early stages, but also induce cancers in late stages. Here, we discuss the activation and inactivation of SMO by different mechanisms to better understand how SMO is regulated by the graded HH signaling activity that eventually governs distinct development outcomes. View Full-Text
Keywords: hedgehog signaling; smoothened; phosphorylation; ubiquitination; cholesterol; phospholipid hedgehog signaling; smoothened; phosphorylation; ubiquitination; cholesterol; phospholipid
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MDPI and ACS Style

Zhang, J.; Liu, Z.; Jia, J. Mechanisms of Smoothened Regulation in Hedgehog Signaling. Cells 2021, 10, 2138. https://doi.org/10.3390/cells10082138

AMA Style

Zhang J, Liu Z, Jia J. Mechanisms of Smoothened Regulation in Hedgehog Signaling. Cells. 2021; 10(8):2138. https://doi.org/10.3390/cells10082138

Chicago/Turabian Style

Zhang, Jie, Zulong Liu, and Jianhang Jia. 2021. "Mechanisms of Smoothened Regulation in Hedgehog Signaling" Cells 10, no. 8: 2138. https://doi.org/10.3390/cells10082138

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