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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 23, 2021 |
| Title |
PKCl/i inhibition activates an ULK2-mediated interferon response to repress tumorigenesis [ATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The interferon (IFN) pathway is critical for cytotoxic T cell activation, which is central to tumor immunosurveillance and successful immunotherapy. We demonstrate here that PKCl/i inactivation results in the hyper-stimulation of the IFN cascade and the enhanced recruitment of CD8+ T cells that impaired the growth of intestinal tumors. PKCl/i directly phosphorylates and represses the activity of ULK2, promoting its degradation through an endosomal microautophagy-driven ubiquitin-dependent mechanism. Loss of PKCl/i results in increased levels of enzymatically active ULK2 that by direct phosphorylation activates TBK1 to foster the activation of the STING-mediated IFN response. PKCl/i inactivation also triggers autophagy that prevents STING degradation by chaperone-mediated autophagy. Thus, PKCl/i is a hub regulating the IFN pathway and three autophagic mechanisms that serve to maintain its homeostatic control. Importantly, single cell multiplex imaging and bioinformatics analysis demonstrated that low PKCl/i levels correlate with enhanced IFN signaling and good prognosis in colorectal cancer patients.
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| Overall design |
ATACseq samples from small intestinal epithelial cells from WT and intestinal epithelial cell-specific atypical PKClambda mice.
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| Contributor(s) |
Linares JF, Zhang X, Martinez-Ordoñez A, Duran A, Kinoshita H, Kasashima H, Nakanishi N, Nakanishi Y, Carelli R, Cappelli L, Arias E, Yahiro M, Ohira M, Patel S, Inghirami G, Loda M, Cuervo AM, Diaz-Meco MT, Moscat J |
| Citation(s) |
34560002, 38092754 |
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| Submission date |
Jul 15, 2021 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Jorge Moscat |
| E-mail(s) |
jom4010@med.cornell.edu
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| Organization name |
WEILL CORNELL MEDICINE
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| Department |
Pathology and Laboratory Medicine
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| Lab |
Moscat and Diaz-Meco
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| Street address |
1188 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE180224 |
PKCl/i inhibition activates an ULK2-mediated interferon response to repress tumorigenesis |
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| Relations |
| BioProject |
PRJNA747048 |
| SRA |
SRP328599 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180223_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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