HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: R600010-JLR200v1 47/7/1352    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, J.-Y. Articles by Hofmann, S. L. Search for Related Content PubMed PubMed Citation Articles by Lu, J.-Y. Articles by Hofmann, S. L. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 1352-1357, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic review series: Lipid Posttranslational Modifications. Lysosomal metabolism of lipid-modified proteins

Jui-Yun Lu and Sandra L. Hofmann¹

Hamon Center for Therapeutic Oncology Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390

Published, JLR Papers in Press, April 20, 2006.

¹ To whom correspondence should be addressed. e-mail: sandra.hofmann{at}utsouthwestern.edu

Much is now understood concerning the synthesis of prenylated and palmitoylated proteins, but what is known of their metabolic fate? This review details metabolic pathways for the lysosomal degradation of S-fatty acylated and prenylated proteins. Central to these pathways are two lysosomal enzymes, palmitoyl-protein thioesterase (PPT1) and prenylcysteine lyase (PCL). PPT1 is a soluble lipase that cleaves fatty acids from cysteine residues in proteins during lysosomal protein degradation. Notably, deficiency in the enzyme causes a neurodegenerative lysosomal storage disorder, infantile neuronal ceroid lipofuscinosis. PCL is a membrane-associated flavin-containing lysosomal monooxygenase that metabolizes prenylcysteine to prenyl aldehyde through a completely novel mechanism. The eventual metabolic fates of other lipidated proteins (such as glycosylphosphatidylinositol-anchored and N-myristoylated proteins) are poorly understood, suggesting directions for future research.

Abbreviations: FAD, flavin adenine dinucleotide; GPI, glycosylphosphatidylinositol; GPI-PLD, glycosylphosphatidylinositol-specific phospholipase D; GROD, granular osmiophilic deposit; INCL, infantile neuronal ceroid lipofuscinosis; MARCKS, myristoylated alanine-rich C kinase substrate; NCL, neuronal ceroid lipofuscinosis; PCL, prenylcysteine lyase; PGAM, peptidylglycine -amidating monooxygenase; PPT1, palmitoyl-protein thioesterase

Supplementary key words posttranslational lipid modifications • lysosomal enzymes • thioesterases • monooxygenases • S-palmitoylation • prenylation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Galluzzo, P. Ascenzi, P. Bulzomi, and M. Marino The Nutritional Flavanone Naringenin Triggers Antiestrogenic Effects by Regulating Estrogen Receptor {alpha}-Palmitoylation Endocrinology, May 1, 2008; 149(5): 2567 - 2575. [Abstract] [Full Text] [PDF]

				N. Makita, J. Sato, P. Rondard, H. Fukamachi, Y. Yuasa, M. A. Aldred, M. Hashimoto, T. Fujita, and T. Iiri Human Gs{alpha} mutant causes pseudohypoparathyroidism type Ia/neonatal diarrhea, a potential cell-specific role of the palmitoylation cycle PNAS, October 30, 2007; 104(44): 17424 - 17429. [Abstract] [Full Text] [PDF]