Asset Details
Do you wish to reserve the book?
Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
Do you wish to request the book?
Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
2017
Overview
It has recently been shown that signal peptide peptidase (SPP) can catalyze the intramembrane cleavage of heme oxygenase-1 (HO-1) that leads to translocation of HO-1 into the cytosol and nucleus. While there is consensus that translocated HO-1 promotes tumor progression and drug resistance, the physiological signals leading to SPP-mediated intramembrane cleavage of HO-1 and the specificity of the process remain unclear. In this study, we used co-immunoprecipitation and confocal laser scanning microscopy to investigate the translocation mechanism of HO-1 and its regulation by SPP. We show that HO-1 and the closely related HO-2 isoenzyme bind to SPP under normoxic conditions. Under hypoxic conditions SPP mediates intramembrane cleavage of HO-1, but not HO-2. In experiments with an inactive HO-1 mutant (H25A) we show that translocation is independent of the catalytic activity of HO-1. Studies with HO-1 / HO-2 chimeras indicate that the membrane anchor, the PEST-domain and the nuclear shuttle sequence of HO-1 are necessary for full cleavage and subsequent translocation under hypoxic conditions. In the presence of co-expressed exogenous SPP, the anchor and the PEST-domain are sufficient for translocation. Taken together, we identified the domains involved in HO-1 translocation and showed that SPP-mediated cleavage is isoform-specific and independent of HO-activity. A closer understanding of the translocation mechanism of HO-1 is of particular importance because nuclear HO-1 seems to lead to tumor progression and drug resistance.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antigens
/ Aspartic Acid Endopeptidases - genetics
/ Aspartic Acid Endopeptidases - metabolism
/ Chimeras
/ Cleavage
/ Cloning
/ Cytosol
/ Genetic Vectors - metabolism
/ Heme
/ Heme oxygenase (decyclizing)
/ Heme Oxygenase (Decyclizing) - chemistry
/ Heme Oxygenase (Decyclizing) - genetics
/ Heme Oxygenase (Decyclizing) - metabolism
/ Heme Oxygenase-1 - chemistry
/ Heme Oxygenase-1 - metabolism
/ Humans
/ Hypoxia
/ Mutant Chimeric Proteins - chemistry
/ Mutant Chimeric Proteins - genetics
/ Mutant Chimeric Proteins - metabolism
/ Mutation
/ Oxidases
/ Peptides
/ Pests
/ Pharmacy
/ Protein Interaction Domains and Motifs
/ Proteins
/ Research and Analysis Methods
/ Rodents
