Premium
Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472 (739.2)
Author(s) -
Hu Yanzhong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.739.2
Subject(s) - phosphorylation , nuclear transport , transcription (linguistics) , microbiology and biotechnology , transcription factor , importin , nuclear protein , threonine , nuclear localization sequence , phosphorylation cascade , biology , serine , protein phosphorylation , chemistry , cell nucleus , biochemistry , protein kinase a , nucleus , gene , linguistics , philosophy
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 it nuclear translocation and transcriptional activity of Hsf4b. Grant Funding Source : national nature sciences foundation of china