Kinetic properties of ASC protein aggregation in epithelial cells
dc.contributor.author | Cheng, Jun | en_US |
dc.contributor.author | Waite, Andrea L. | en_US |
dc.contributor.author | Tkaczyk, Eric Robert | en_US |
dc.contributor.author | Ke, Kevin | en_US |
dc.contributor.author | Richards, Neil | en_US |
dc.contributor.author | Hunt, Alan J. | en_US |
dc.contributor.author | Gumucio, Deborah L. | en_US |
dc.date.accessioned | 2010-01-05T15:11:37Z | |
dc.date.available | 2011-03-01T16:26:42Z | en_US |
dc.date.issued | 2010-03 | en_US |
dc.identifier.citation | Cheng, Jun; Waite, Andrea L.; Tkaczyk, Eric R.; Ke, Kevin; Richards, Neil; Hunt, Alan J.; Gumucio, Deborah L. (2010). "Kinetic properties of ASC protein aggregation in epithelial cells Jun Cheng and Andrea L. Waite contributed equally to this work. ." Journal of Cellular Physiology 222(3): 738-747. <http://hdl.handle.net/2027.42/64555> | en_US |
dc.identifier.issn | 0021-9541 | en_US |
dc.identifier.issn | 1097-4652 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/64555 | |
dc.description.abstract | A poptosis-associated s peck-like protein with C ARD domain (ASC), an adaptor protein composed of caspase recruitment and pyrin domains, can efficiently self-associate to form a large spherical structure, called a speck. Although ASC aggregation is generally involved with both inflammatory processes and apoptosis, the detailed dynamics of speck formation have not been characterized. In this report, speck formation in HeLa cells transfected with ASC is examined by time-lapse live-imaging by confocal laser scanning microscopy. The results show that ASC aggregation is a very rapid and tightly regulated process. Prior to speck formation, soluble ASC aggregation is a low probability event, and the affinity of ASC subunits for one another is very low. Following a speck nucleation event, the affinity for further addition of ASC subunits increases dramatically, and aggregation is a highly energetically favorable reaction (Gibbs free energy ∼ −40 kJ/mol). This leads to a rapid depletion of soluble ASC, making it highly unlikely that a second speck will form inside the same cell and assuring that speck formation is “all or none,” with a well-defined end point. Comparison with kinetic models of the aggregation process indicates diffusion, instead of active transport, is the dominant process for speck growth. Though speck formation and aggresome formation share some properties, we show that the two processes are distinct. J. Cell. Physiol. 222: 738–747, 2010. © 2009 Wiley-Liss, Inc. | en_US |
dc.format.extent | 539274 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cell & Developmental Biology | en_US |
dc.title | Kinetic properties of ASC protein aggregation in epithelial cells | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbsecondlevel | Kinesiology and Sports | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan ; Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan ; Associate Professor, Department of Biomedical Engineering, University of Michigan College of Engineering, 1101 Beal Avenue, Box 2170, Ann Arbor, MI 48109-2099. | en_US |
dc.contributor.affiliationum | Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan ; Professor, Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Box 2200, Ann Arbor, MI 48109-2200. | en_US |
dc.identifier.pmid | 20020448 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/64555/1/22005_ftp.pdf | |
dc.identifier.doi | 10.1002/jcp.22005 | en_US |
dc.identifier.source | Journal of Cellular Physiology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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