Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472

Jun Zhang, Zengyi Ma, Jiyan Wang, Shulian Li, Yaqin Zhang, Yuelin Wang, Mingli Wang, Xiaoli Feng, Xiang Liu, Guangchao Liu, Qiang Lou, Xiukun Cui, Yuanfang Ma, Zheng Dong, Yan zhong Hu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Hsf4b, a key regulator of postnatal lens development, is subjected to posttranslational modifications including phosphorylation. However, the phosphorylation sites in Hsf4b and their biological effects on the transcription activity of Hsf4b are poorly understood. Here we examined 17 potential phosphorylation residues in Hsf4b with alanine-scanning assays and found that a T472A mutation diminished Hsf4b-mediated expression of Hsp25 and αB-crystallin. In contrast, the phosphomimetic mutation of T472D enhanced their expression. Further investigation demonstrated that Hsf4b could interact with nuclear-transporter importin β-1 and Hsc70 via amino acids 246-320 and 320-493, respectively. T472A mutation reduced Hsf4b's interaction with importin β-1, while enhancing its interaction with Hsc70, resulting in Hsf4b cytosolic re-localization, protein instability and transcription activity attenuation. At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphorylation of Hsf4b at T472 by protein kinases such as MEK6 regulates Hsf4b interaction with the importin β-1-Hsc70 complex, resulting in blockade of its nuclear translocation and transcriptional activity of Hsf4b.

Original languageEnglish (US)
Pages (from-to)580-589
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Hsc70
  • Hsf4b
  • Importin β-1
  • MEK6
  • Phosphorylation
  • T472

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Zhang, J., Ma, Z., Wang, J., Li, S., Zhang, Y., Wang, Y., Wang, M., Feng, X., Liu, X., Liu, G., Lou, Q., Cui, X., Ma, Y., Dong, Z., & Hu, Y. Z. (2014). Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472. Biochimica et Biophysica Acta - Molecular Cell Research, 1843(3), 580-589. https://doi.org/10.1016/j.bbamcr.2013.12.008