Nature cell biology, 2020-12, Vol.22 (12), p.1447-1459
2020
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- Autor(en) / Beteiligte
- Titel
- Heat stress activates YAP/TAZ to induce the heat shock transcriptome
- Ist Teil von
- Nature cell biology, 2020-12, Vol.22 (12), p.1447-1459
- Ort / Verlag
- England
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The Hippo pathway plays critical roles in cell growth, differentiation, organ development and tissue homeostasis, whereas its dysregulation can lead to tumorigenesis. YAP and TAZ are transcription co-activators and represent the main downstream effectors of the Hippo pathway. Here, we show that heat stress induces a strong and rapid YAP dephosphorylation and activation. The effect of heat shock on YAP is dominant to other signals known to modulate the Hippo pathway. Heat shock inhibits LATS kinase by promoting HSP90-dependent LATS interaction with and inactivation by protein phosphatase 5. Heat shock also induces LATS ubiquitination and degradation. YAP and TAZ are crucial for cellular heat shock responses, including the heat shock transcriptome and cell viability. This study uncovers previously unknown mechanisms of Hippo regulation by heat shock, as well as physiological functions of YAP, in the heat stress response. Our observations also reveal a potential combinational therapy involving hyperthermia and targeting of the Hippo pathway.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1465-7392eISSN: 1476-4679DOI: 10.1038/s41556-020-00602-9Titel-ID: cdi_pubmed_primary_33199845
- Format
- –
- Schlagworte
- A549 Cells, Adaptor Proteins, Signal Transducing - genetics, Adaptor Proteins, Signal Transducing - metabolism, Animals, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Line, Tumor, Cell Survival - genetics, Female, Gene Expression Profiling - methods, Heat-Shock Response - genetics, HEK293 Cells, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, NIH 3T3 Cells, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Phosphoprotein Phosphatases - genetics, Phosphoprotein Phosphatases - metabolism, Phosphorylation, Protein Serine-Threonine Kinases - genetics, Protein Serine-Threonine Kinases - metabolism, Signal Transduction - genetics, Trans-Activators - genetics, Trans-Activators - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Transcriptome - genetics, YAP-Signaling Proteins