Scientific article

Multiple Layers of Regulation of Human Heat Shock Transcription Factor 1

Published inMolecular and cellular biology, vol. 15, no. 8, p. 4319-4330
Publication date2023-03-30
First online date2023-03-30

Upon heat stress, monomeric human heat shock transcription factor 1 (hHSF1) is converted to a trimer, acquires DNA-binding ability, is transported to the nucleus, and becomes transcriptionally competent. It was not known previously whether these regulatory changes are caused by a single activation event or whether they occur independently from one another, providing a multilayered control that may prevent inadvertant activation of hHSF1. Comparison of wild-type and mutant hHSF1 expressed in Xenopus oocytes and human HeLa cells suggested that retention of hHSF1 in the monomeric form depends on hydrophobic repeats (LZ1 to LZ3) and a carboxy-terminal sequence element in hHSF1 as well as on the presence of a titratable factor in the cell. Oligomerization of hHSF1 appears to induce DNA-binding activity as well as to uncover an amino-terminally located nuclear localization signal. A mechanism distinct from that controlling oligomerization regulates the transcriptional competence of hHSF1. Components of this mechanism were mapped to a region, including LZ2 and nearby sequences downstream from LZ2, that is clearly separated from the carboxy-terminally located transcription activation domain(s). We propose the existence of a fold-back structure that masks the transcription activation domain in the unstressed cell but is opened up by modification of hHSF1 and/or binding of a factor facilitating hHSF1 unfolding in the stressed cell. Activation of hHSF1 appears to involve at least two independently regulated structural transitions.

Citation (ISO format)
ZUO, Jianru, RUNGGER, Duri, VOELLMY, Richard. Multiple Layers of Regulation of Human Heat Shock Transcription Factor 1. In: Molecular and cellular biology, 2023, vol. 15, n° 8, p. 4319–4330. doi: 10.1128/MCB.15.8.4319
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Article (Published version)
ISSN of the journal0270-7306

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