[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity
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Abstract
- The yeast prion [SWI+], formed of heritable amyloid aggregates of the Swi1 protein, results in a partial loss of function of the SWI/SNF chromatin-remodeling complex, required for the regulation of a diverse set of genes. Our genetic analysis revealed that [SWI+] propagation is highly dependent upon the action of members of the Hsp70 molecular chaperone system, specifically the Hsp70 Ssa, two of its J-protein co-chaperones, Sis1 and Ydj1, and the nucleotide exchange factors of the Hsp110 family ( Sse1/2). Notably, while all yeast prions tested thus far require Sis1, [SWI+] is the only one known to require the activity of Ydj1, the most abundant J-protein in yeast. The C-terminal region of Ydj1, which contains the client protein interaction domain, is required for [SWI+] propagation. However, Ydj1 is not unique in this regard, as another, closely related J-protein, Apj1, can substitute for it when expressed at a level approaching that of Ydj1. While dependent upon Ydj1 and Sis1 for propagation, [SWI+] is also highly sensitive to overexpression of both J-proteins. However, this increased prion-loss requires only the highly conserved 70 amino acid J-domain, which serves to stimulate the ATPase activity of Hsp70 and thus to stabilize its interaction with client protein. Overexpression of the J-domain from Sis1, Ydj1, or Apj1 is sufficient to destabilize [SWI+]. In addition, [SWI+] is lost upon overexpression of Sse nucleotide exchange factors, which act to destabilize Hsp70's interaction with client proteins. Given the plethora of genes affected by the activity of the SWI/SNF chromatin-remodeling complex, it is possible that this sensitivity of [SWI+] to the activity of Hsp70 chaperone machinery may serve a regulatory role, keeping this prion in an easily-lost, meta-stable state. Such sensitivity may provide a means to reach an optimal balance of phenotypic diversity within a cell population to better adapt to stressful environments.
Title | [SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity |
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Creator | Craig, E. A. |
Du, Z. | |
Higurashi, T. | |
Li, X. | |
Li, L. | |
Hines, Justin K. | |
Publisher | PLoS Genetics |
Academic Department | Chemistry |
Division | Natural Sciences |
Organization | Lafayette College |
Date Issued | February 2011 |
Date Available | 2014-04-15T20:46:30Z |
Type | Article |
Language | English |
Bibliographic Citation | Hines, J. K., et al. (2011 Feb.) "[SWI+], the prion formed by the chromatin remodeling factor Swi1, is highly sensitive to alterations in Hsp70 chaperone system activity." PLoS Genetics 7 (2): e1001309. |
Standard Identifier | DOI 10.1371/journal.pgen.1001309 |
Handle 10385/1446 | |
Permalink | http://hdl.handle.net/10385/1446 |
Rights Statement | Creative Commons - Attribution |
Rights Holders | Craig, E. A. |
Du, Z. | |
Higurashi, T. | |
Li, X. | |
Li, L. | |
Hines, Justin K. |
Contains
File | Hines-PLoSGenetics-vol7-2011.pdf | Uploaded 2019-10-20 | Public | Download |