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| Status |
Public on Aug 31, 2024 |
| Title |
Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cyclic GMP-AMP synthase (cGAS) binds pathogenic and other cytoplasmic double-stranded DNA (dsDNA) to catalyze the synthesis of cyclic GMP-AMP (cGAMP), which serves as the secondary messenger to activate the STING pathway and innate immune responses. Emerging evidence suggests that activation of the cGAS pathway is crucial for anti-tumor immunity, however, no effective intervention method targeting cGAS is currently available. Here we report that cGAS is palmitoylated by ZDHHC9 at cysteines 404/405, which promotes the dimerization and activation of cGAS. We further identified that lysophospholipase-like 1 (LYPLAL1) depalmitoylates cGAS to compromise its normal function. As such, inhibition of LYPLAL1 significantly enhances cGAS-mediated innate immune response, elevates PD-L1 expression and enhances anti-tumor response to PD-1 blockade. Our results therefore reveal that targeting LYPLAL1-mediated cGAS depalmitoylation contributes to cGAS activation, providing a potential strategy to augment the efficacy of anti-tumor immunotherapy.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for 4T-1 wild-type cells and Lyplal1 knockout cells.
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| Contributor(s) |
Fan Y, Yang G, Wei W, Li L |
| Citation missing |
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| Submission date |
Aug 30, 2023 |
| Last update date |
Aug 31, 2024 |
| Contact name |
Yizeng Fan |
| E-mail(s) |
fyz19910701@xjtufh.edu.cn
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| Organization name |
Xi'an Jiaotong University
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| Street address |
Yanta West Road
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| City |
Xi'an |
| ZIP/Postal code |
710061 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1010803 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241952_Mus_TPM_raw.txt.gz |
906.4 Kb |
(ftp)(http) |
TXT |
| GSE241952_RAW.tar |
3.0 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE241952_allsample_featureCounts.txt.gz |
413.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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