A small molecule-directed approach to control protein localization and function
dc.contributor.author | Geda, Prasanthi | en_US |
dc.contributor.author | Patury, Srikanth | en_US |
dc.contributor.author | Ma, Jun | en_US |
dc.contributor.author | Bharucha, Nike N. | en_US |
dc.contributor.author | Dobry, Craig J. | en_US |
dc.contributor.author | Lawson, Sarah K. | en_US |
dc.contributor.author | Gestwicki, Jason E. | en_US |
dc.contributor.author | Kumar, Anuj | en_US |
dc.date.accessioned | 2008-08-27T20:04:37Z | |
dc.date.available | 2009-10-02T17:27:37Z | en_US |
dc.date.issued | 2008-08 | en_US |
dc.identifier.citation | Geda, Prasanthi; Patury, Srikanth; Ma, Jun; Bharucha, Nike; Dobry, Craig J.; Lawson, Sarah K.; Gestwicki, Jason E.; Kumar, Anuj (2008). "A small molecule-directed approach to control protein localization and function." Yeast 25(8): 577-594. <http://hdl.handle.net/2027.42/60901> | en_US |
dc.identifier.issn | 0749-503X | en_US |
dc.identifier.issn | 1097-0061 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60901 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18668531&dopt=citation | en_US |
dc.description.abstract | Protein localization is tightly linked with function, such that the subcellular distribution of a protein serves as an important control point regulating activity. Exploiting this regulatory mechanism, we present here a general approach by which protein location, and hence function, may be controlled on demand in the budding yeast. In this system a small molecule, rapamycin, is used to temporarily recruit a strong cellular address signal to the target protein, placing subcellular localization under control of the selective chemical stimulus. The kinetics of this system are rapid: rapamycin-directed nucleo-cytoplasmic transport is evident 10–12 min post-treatment and the process is reversible upon removal of rapamycin. Accordingly, we envision this platform as a promising approach for the systematic construction of conditional loss-of-function mutants. As proof of principle, we used this system to direct nuclear export of the essential heat shock transcription factor Hsf1p, thereby mimicking the cell-cycle arrest phenotype of an hsf1 temperature-sensitive mutant. Our drug-induced localization platform also provides a method by which protein localization can be uncoupled from endogenous cell signalling events, addressing the necessity or sufficiency of a given localization shift for a particular cell process. To illustrate, we directed the nuclear import of the calcineurin-dependent transcription factor Crz1p in the absence of native stimuli; this analysis directly substantiates that nuclear translocation of this protein is insufficient for its transcriptional activity. In total, this technology represents a powerful method for the generation of conditional alleles and directed mislocalization studies in yeast, with potential applicability on a genome-wide scale. Copyright © 2008 John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 1365602 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | A small molecule-directed approach to control protein localization and function | 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.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA | en_US |
dc.contributor.affiliationum | Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA ; The Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA ; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA. | en_US |
dc.identifier.pmid | 18668531 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60901/1/yea_1610_sm_supportinginformations.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/yea.1610 | en_US |
dc.identifier.source | Yeast | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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