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| Status |
Public on Jul 18, 2024 |
| Title |
An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Heat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified JMJD6 as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a non-canonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis. In a positive feedback circuit, HSF1 binds and promotes JMJD6 expression, which in turn reduces HSP70 R469 monomethylation to disrupt HSP70-HSF1 repressive complexes resulting in enhanced HSF1 activation. Thus, JMJD6 is intricately wired into the proteostasis network where it plays a critical role for cellular adaptation to proteotoxic stress.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for PC3M cells transfected with siNT or siJMJD6 and PC3M HSF1 KO cell lines treated with either DMSO or MG132 (2.5uM) for 4 hours. Comparative gene expression profiling analysis of RNA-seq data for PC3M cells transfected with siNT or siJMJD6 and exposed to heat shock at 42C for 1h and recovered for 2 hours.
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| Contributor(s) |
Alasady MJ, Koeva M, Takagishi SR, Segal D, Amici DR, Smith RS, Anse DJ, Lindquist S, Whitesell L, Bartom ET, Taipale M, Mendillo ML |
| Citation(s) |
38985769 |
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| Submission date |
Jun 24, 2024 |
| Last update date |
Jul 18, 2024 |
| Contact name |
Marc L Mendillo |
| E-mail(s) |
[email protected]
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| Phone |
3125034862
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| Organization name |
Northwestern University
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| Department |
Biochemistry and Molecular Genetics
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| Lab |
Marc Mendillo
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| Street address |
303 East Superior Street Simpson Querrey, 7th Floo
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA1127665 |
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