ArticleProceedings of the National Academy of Sciences of the United States of America2007
Composite synthetic lethal identification of membrane traffic inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The AP-1 adaptor complex is required for cell surface modifications and the survival ofInfection and immunity · 2026Article
- The AP-1 adaptor complex is essential for intracellular trafficking of the ORF2 capsid protein and assembly of Hepatitis E virus.Cellular and molecular life sciences : CMLS · 2024Article
- Chemical Manipulation of the Endosome Trafficking Machinery: Implications for Oligonucleotide Delivery.Biomedicines · 2021Review
- A simple and inexpensive quantitative technique for determining chemical sensitivity in Saccharomyces cerevisiae.Scientific reports · 2018Article
- Adaptor Protein 1A Facilitates Dengue Virus Replication.PloS one · 2015Article
- A small molecule inhibitor of redox-regulated protein translocation into mitochondria.Developmental cell · 2013Article
- Receptors, endocytosis, and trafficking: the biological basis of targeted delivery of antisense and siRNA oligonucleotides.Journal of drug targeting · 2013Review
- Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins.Molecular biology of the cell · 2012Article
- Regulated vesicular trafficking of specific PCDH15 and VLGR1 variants in auditory hair cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Article
- Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Rapid inactivation of proteins by rapamycin-induced rerouting to mitochondria.Developmental cell · 2010Article
- A chemical genetic screen for modulators of exocytic transport identifies inhibitors of a transport mechanism linked to GTR2 function.Eukaryotic cell · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Small molecule inhibitors provide powerful tools to characterize highly dynamic and complex eukaryotic cell pathways such as those mediating membrane traffic. However, a lack of easy and generalizable assays has constrained identification of novel inhibitors despite availability of diverse chemical libraries. Here, we report a facile growth-based strategy in yeast to screen for pathway-specific inhibitors. The approach uses well characterized synthetic genetic growth defects to guide design of cells genetically sensitized for inhibition of chosen pathways. With this strategy, we identified a family of piperazinyl phenylethanone compounds as inhibitors of traffic between the trans-Golgi network (TGN) and endosomes that depends on the clathrin adaptor complex AP-1. The compounds did not significantly alter other trafficking pathways involving the TGN or endosomes, indicating specificity. Compound treatment also altered localization of AP-1 in mammalian cells. These previously uncharacterized inhibitors will be useful for future studies of clathrin-mediated transport in yeast, and potentially in other organisms. Furthermore, the easily automated technology should be adaptable for identification of inhibitors of other cellular processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.