doi: 10.1126/science.274.5285.255.
Cholesterol modification of hedgehog signaling proteins in animal development
Affiliations
- PMID:8824192
- DOI: 10.1126/science.274.5285.255
Item in Clipboard
Cholesterol modification of hedgehog signaling proteins in animal development
J A Porter et al. Science..
Display options
Format
Display options
Format
Erratum in
- Science 1996 Dec 6;274(5293):1597
Abstract
Hedgehog (Hh) proteins comprise a family of secreted signaling molecules essential for patterning a variety of structures in animal embryogenesis. During biosynthesis, Hh undergoes an autocleavage reaction, mediated by its carboxyl-terminal domain, that produces a lipid-modified amino-terminal fragment responsible for all known Hh signaling activity. Here it is reported that cholesterol is the lipophilic moiety covalently attached to the amino-terminal signaling domain during autoprocessing and that the carboxyl-terminal domain acts as an intramolecular cholesterol transferase. This use of cholesterol to modify embryonic signaling proteins may account for some of the effects of perturbed cholesterol biosynthesis on animal development.
Comment in
- Pass the butter..Martin G.Martin G.Science. 1996 Oct 11;274(5285):203-4. doi: 10.1126/science.274.5285.203.Science. 1996.PMID:8927979Review.No abstract available.
Similar articles
- Pass the butter..Martin G.Martin G.Science. 1996 Oct 11;274(5285):203-4. doi: 10.1126/science.274.5285.203.Science. 1996.PMID:8927979Review.No abstract available.
- Cholesterol modification of proteins.Mann RK, Beachy PA.Mann RK, et al.Biochim Biophys Acta. 2000 Dec 15;1529(1-3):188-202. doi: 10.1016/s1388-1981(00)00148-7.Biochim Biophys Acta. 2000.PMID:11111088Review.
- Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain.Porter JA, Ekker SC, Park WJ, von Kessler DP, Young KE, Chen CH, Ma Y, Woods AS, Cotter RJ, Koonin EV, Beachy PA.Porter JA, et al.Cell. 1996 Jul 12;86(1):21-34. doi: 10.1016/s0092-8674(00)80074-4.Cell. 1996.PMID:8689684
- Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia.Gallet A, Ruel L, Staccini-Lavenant L, Thérond PP.Gallet A, et al.Development. 2006 Feb;133(3):407-18. doi: 10.1242/dev.02212. Epub 2006 Jan 5.Development. 2006.PMID:16396912
- Autoproteolysis in hedgehog protein biogenesis.Lee JJ, Ekker SC, von Kessler DP, Porter JA, Sun BI, Beachy PA.Lee JJ, et al.Science. 1994 Dec 2;266(5190):1528-37. doi: 10.1126/science.7985023.Science. 1994.PMID:7985023
Cited by
- Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer.Bordeau BM, Ciulla DA, Callahan BP.Bordeau BM, et al.ChemMedChem. 2016 Sep 20;11(18):1983-6. doi: 10.1002/cmdc.201600238. Epub 2016 Jul 20.ChemMedChem. 2016.PMID:27435344Free PMC article.
- Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals.Palm W, Swierczynska MM, Kumari V, Ehrhart-Bornstein M, Bornstein SR, Eaton S.Palm W, et al.PLoS Biol. 2013;11(3):e1001505. doi: 10.1371/journal.pbio.1001505. Epub 2013 Mar 12.PLoS Biol. 2013.PMID:23554573Free PMC article.
- Glial Hedgehog signalling and lipid metabolism regulate neural stem cell proliferation in Drosophila.Dong Q, Zavortink M, Froldi F, Golenkina S, Lam T, Cheng LY.Dong Q, et al.EMBO Rep. 2021 May 5;22(5):e52130. doi: 10.15252/embr.202052130. Epub 2021 Mar 10.EMBO Rep. 2021.PMID:33751817Free PMC article.
- A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications.Suazo KF, Park KY, Distefano MD.Suazo KF, et al.Chem Rev. 2021 Jun 23;121(12):7178-7248. doi: 10.1021/acs.chemrev.0c01108. Epub 2021 Apr 6.Chem Rev. 2021.PMID:33821625Free PMC article.Review.
- Hedgehog Pathway Activation Requires Coreceptor-Catalyzed, Lipid-Dependent Relay of the Sonic Hedgehog Ligand.Wierbowski BM, Petrov K, Aravena L, Gu G, Xu Y, Salic A.Wierbowski BM, et al.Dev Cell. 2020 Nov 23;55(4):450-467.e8. doi: 10.1016/j.devcel.2020.09.017. Epub 2020 Oct 9.Dev Cell. 2020.PMID:33038332Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases