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Molecular and Cellular Biology, April 2006, p. 3282-3294, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3282-3294.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Association and Regulation of Heat Shock Transcription Factor 4b with both Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and Dual-Specificity Tyrosine Phosphatase DUSP26

Yanzhong Hu and Nahid F. Mivechi*

Molecular Chaperone Biology/Radiobiology Program, Medical College of Georgia, 1120 15th St., CB2803, Augusta, Georgia 30912

Received 1 August 2005/ Returned for modification 30 September 2005/ Accepted 23 January 2006

The heat shock transcription factors (Hsfs) activate the stress-inducible expression of heat shock proteins (Hsps) and other molecular chaperones in response to stress and, therefore, play an essential role in protein disaggregation and protein folding. In humans, missense mutation in the hsf4 gene causes cataract, and mice bearing a targeted disruption of the hsf4 gene exhibit defects in lens fiber cell differentiation and early cataract formation. Here, we show that Hsf4b is a direct target of the mitogen-activated protein (MAP) kinase extracellular signal-related kinase (ERK) and that phosphorylation of Hsf4b by ERK leads to increased ability of Hsf4b to bind DNA. Surprisingly, Hsf4b also interacts with an ERK-specific dual-specificity tyrosine phosphatase named DUSP26 identified from a yeast two-hybrid screen. While activated ERK phosphorylates Hsf4b, DUSP26 controls the activity of ERK, leading to phosphorylation/dephosphorylation of Hsf4b, altering its ability to bind DNA. Therefore, DUSP26 interaction with Hsf4b places this transcription factor within a regulatory circuit in the MAP kinase signaling pathway.


* Corresponding author. Mailing address: Molecular Chaperone Biology/Radiobiology Program, Medical College of Georgia, 1120 15th St., CB2803, Augusta, GA 30912. Phone: (706) 721-8759. Fax: (706) 721-8752. E-mail: mivechi{at}immag.mcg.edu.


Molecular and Cellular Biology, April 2006, p. 3282-3294, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3282-3294.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

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  • Ostling, P., Bjork, J. K., Roos-Mattjus, P., Mezger, V., Sistonen, L. (2007). Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1. J. Biol. Chem. 282: 7077-7086 [Abstract] [Full Text]