Browse by author
Lookup NU author(s): Dr Ralph Jans
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Type I transglutaminase (TG1) is an enzyme that is responsible for assembly of the keratinocyte cornified envelope. Although TG1 mutation is an underlying cause of autosomal recessive congenital ichthyosis, a debilitating skin disease, the pathogenic mechanism is not completely understood. In the present study we show that TG1 is an endoplasmic reticulum (ER) membrane-associated protein that is trafficked through the ER for ultimate delivery to the plasma membrane. Mutation severely attenuates this processing and a catalytically inactive point mutant, TG1-FLAG(C377A), accumulates in the endoplasmic reticulum and in aggresome-like structures where it is ubiquitinylated. This accumulation results from protein misfolding, as treatment with a chemical chaperone permits it to exit the endoplasmic reticulum and travel to the plasma membrane. ER accumulation is also observed for ichthyosis-associated TG1 mutants. Our findings suggest that misfolding of TG1 mutants leads to ubiquitinylation and accumulation in the ER and aggresomes, and that abnormal intracellular processing of TG1 mutants may be an underlying cause of ichthyosis. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Author(s): Jiang H, Jans R, Xu W, Rorke E, Lin C, Chen Y, Fang S, Zhong Y, Eckert R
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Year: 2010
Volume: 285
Issue: 41
Pages: 31634-31646
Print publication date: 27/07/2010
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
URL: http://dx.doi.org/10.1074/jbc.M110.128645
DOI: 10.1074/jbc.M110.128645
PubMed id: 20663883
Altmetrics provided by Altmetric
