@article{5d0dec6b35d14ad989cebabfa95008ad,
title = "Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling",
abstract = "Cell differentiation and proliferation require Hedgehog (HH) signaling and aberrant HH signaling causes birth defects or cancers. In this signaling pathway, the N-terminally palmitoylated and C-terminally cholesterylated HH ligand is secreted into the extracellular space with help of the Dispatched-1 (DISP1) and Scube2 proteins. The Patched-1 (PTCH1) protein releases its inhibition of the oncoprotein Smoothened (SMO) after binding the HH ligand, triggering downstream signaling events. In this review, we discuss the recent structural and biochemical studies on four major components of the HH pathway: the HH ligand, DISP1, PTCH1, and SMO. This research provides mechanistic insights into how HH signaling is generated and transduced from the cell surface into the intercellular space and will aid in facilitating the treatment of HH-related diseases.",
keywords = "Dispatched, Hedgehog, Patched, Smoothened, signal transduction, sterol",
author = "Xiaofeng Qi and Xiaochun Li",
note = "Funding Information: We apologize to our colleagues whose work has not been mentioned owing to space limitations. We thank E. Coutavas, L. Friedberg, J. Jiang, and P. Schmiege for their time and efforts on the manuscript preparation. This work was supported by NIH grants R01 GM135343 and P01 HL020948 . X.Q. is the recipient of DDBrown Fellow of the Life Sciences Research Foundation. X.L. is a Damon Runyon-Rachleff Innovator supported by the Damon Runyon Cancer Research Foundation ( DRR-53-19 ) and a Rita C. and William P. Clements, Jr Scholar in Biomedical Research at UT Southwestern Medical Center. Funding Information: We apologize to our colleagues whose work has not been mentioned owing to space limitations. We thank E. Coutavas, L. Friedberg, J. Jiang, and P. Schmiege for their time and efforts on the manuscript preparation. This work was supported by NIH grants R01 GM135343 and P01 HL020948. X.Q. is the recipient of DDBrown Fellow of the Life Sciences Research Foundation. X.L. is a Damon Runyon-Rachleff Innovator supported by the Damon Runyon Cancer Research Foundation (DRR-53-19) and a Rita C. and William P. Clements, Jr Scholar in Biomedical Research at UT Southwestern Medical Center. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = may,
doi = "10.1016/j.tibs.2020.01.006",
language = "English (US)",
volume = "45",
pages = "397--410",
journal = "Trends in Biochemical Sciences",
issn = "0376-5067",
publisher = "Elsevier Limited",
number = "5",
}