The endomembrane system in mammalian cells has evolved over the past two billion years from a simple endocytic pathway in a single-celled primordial ancestor to complex networks supporting multicellular structures that form metazoan tissue and organ systems. The increased organellar complexity of metazoan cells requires additional trafficking machinery absent in yeast or other unicellular organisms to maintain organ homoeostasis and to process the signals that control proliferation, differentiation or the execution of cell death programmes. The PACS (phosphofurin acidic cluster sorting) proteins are one such family of multifunctional membrane traffic regulators that mediate organ homoeostasis and have important roles in diverse pathologies and disease states. This review summarizes our current knowledge of the PACS proteins, including their structure and regulation in cargo binding, their genetics, their roles in secretory and endocytic pathway traffic, interorganellar communication and how cell-death signals reprogramme the PACS proteins to regulate apoptosis. We also summarize our current understanding of how PACS genes are dysregulated in cancer and how viral pathogens ranging from HIV-1 to herpesviruses have evolved to usurp the PACS sorting machinery to promote virus assembly, viral spread and immunoevasion.
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July 2009
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June 12 2009
At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis Available to Purchase
Robert T. Youker;
Robert T. Youker
*Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, U.S.A.
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Ujwal Shinde;
Ujwal Shinde
†Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, U.S.A.
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Robert Day;
Robert Day
‡Department of Pharmacology, University of Sherbrooke, 3001 12e Avenue Nord, Quebec, Quebec Province, J1H 5N4, Canada
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Gary Thomas
Gary Thomas
1
*Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 23 2008
Accepted:
June 11 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 421 (1): 1–15.
Article history
Received:
May 23 2008
Accepted:
June 11 2008
Citation
Robert T. Youker, Ujwal Shinde, Robert Day, Gary Thomas; At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis. Biochem J 1 July 2009; 421 (1): 1–15. doi: https://doi.org/10.1042/BJ20081016
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