Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA990673 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25114102_1.fastq.gz | Fastqsanger.gz | |||
| SRR25114102_2.fastq.gz | Fastqsanger.gz | |||
| SRR25114103_1.fastq.gz | Fastqsanger.gz | |||
| SRR25114103_2.fastq.gz | Fastqsanger.gz | |||
| SRR25114104_1.fastq.gz | Fastqsanger.gz |
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Project description:Piezo2 impedes stemness maintenance of CD8+ T cells by downregulating IL-15 production after radiotherapy, thereby leading to cancer radioresistance.
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Project description:Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance
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Project description:Protein kinase A is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity of nociceptive sensory afferent. Here we examine the molecular mechanism underlying protein kinase-Adependent modulation of the mechanically-activated ion channel PIEZO2, which confers mechanosensitivity to many nociceptors. Using phosphorylation site prediction algorithms, we identified multiple putative and highly conserved PKA phosphorylation sites located on intracellular intrinsically disordered regions of PIEZO2. Site-directed mutagenesis and patch-clamp recordings showed that substitution of one or multiple putative PKA sites within a single intracellular domains does not alter PKA-induced PIEZO2 sensitization, whereas mutation of a combination of nine putative sites located on four different intracellular regions completely abolishes PKA-dependent PIEZO2 modulation, suggesting that the effect requires multisite phosphorylation. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveals a previously unrecognized functional difference between PIEZO1 and PIEZO2. Moreover, by demonstrating that PKA only modulates PIEZO2 currents evoked by focal mechanical indentation of the cell, but not currents evoked by pressure-induced membrane stretch, we provide evidence suggesting that PIEZO2 is a polymodal mechanosensor that engages different protein domains for detecting different types of mechanical stimuli.
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