| 2017 |
A de novo partial loss-of-function mutation in PRKCE (PKCε) causes SHORT syndrome by impairing mTORC2-dependent AKT activation. The mutant PKCε bound to the mTORC2 component SIN1 with higher affinity than wild-type, altered mTORC2-dependent priming dynamics, and caused impaired mTORC2-dependent pAKT-S473 following rapamycin treatment, as well as reduced pFOXO1-S256 and pS6-S240/244 in patient lymphoblasts. Interaction with PDK1 and SIN1 was preserved in the mutant. |
Whole exome sequencing, kinase activity assay, phospho-specific antibody immunoblotting in patient lymphoblasts and HEK293 ectopic expression, co-immunoprecipitation of PDK1/SIN1 interactions |
Human molecular genetics |
High |
28934384
|
| 2017 |
PRKCE is a direct target of miR-218-5p: miR-218-5p overexpression repressed luciferase activity of reporter constructs containing the 3'-UTR of PRKCE and reduced PRKCE protein expression. PRKCE promotes gemcitabine resistance in gallbladder cancer cells through upregulation of MDR1/P-glycoprotein. |
Luciferase 3'-UTR reporter assay, miRNA overexpression/knockdown, Western blotting, cell viability assays |
Cell death & disease |
Medium |
28492560
|
| 2013 |
miR-146a directly binds the 3'-UTR of PRKCE (confirmed by luciferase reporter assay) and decreases PKCε protein levels in papillary thyroid carcinoma cells, leading to increased apoptosis and suppressed tumor growth in a subcutaneous xenograft model. PKCε acts downstream of the Ras/Raf-1 pathway and inhibits mitochondrial apoptosis in thyroid cancer cells. |
Luciferase 3'-UTR reporter assay, miR-146a stable overexpression, Western blotting, apoptosis assays, xenograft tumor growth |
International journal of cancer |
Medium |
23457043
|
| 2020 |
miR-205-5p directly targets PRKCE (validated by luciferase reporter assay) and negatively regulates its expression in gallbladder cancer stem cells. Overexpression of miR-205-5p or silencing of PRKCE inhibited drug resistance, proliferation, and colony formation while promoting apoptosis, and attenuated gemcitabine resistance in vivo. |
Luciferase 3'-UTR reporter assay, miRNA overexpression, PRKCE knockdown, apoptosis assays (Bax, Bcl-2, cleaved caspase 3 Western blot), mouse xenograft model |
Bioscience reports |
Medium |
32869841
|
| 2011 |
Deletion of Prkce in mice protects against diet-induced glucose intolerance via two temporally distinct mechanisms: (1) early protection via altered hepatic lipid partitioning that reduces fatty acid catabolism-derived reactive oxygen species (ROS), and (2) later enhancement of glucose-stimulated insulin secretion. Prkce-/- hepatocytes showed reduced ROS production in the presence of palmitate and altered mitochondrial oxidative capacity. |
Prkce knockout mice on high-fat diet, glucose tolerance tests, indirect calorimetry, iTRAQ quantitative proteomics, immunoblotting, primary hepatocyte assays, mitochondrial oxidative capacity measurements |
Diabetologia |
High |
21347625
|
| 2008 |
Fetal cocaine exposure programs cardiac Prkce gene repression in adult male rat offspring via DNA methylation of two Sp1 binding sites (-346 and -268) in the Prkce promoter. Methylation of these sites decreased SP1 binding affinity to the promoter, and reporter gene assays confirmed both Sp1 sites have a strong stimulatory role in Prkce gene activity. The effect was sex-dependent (males but not females showed decreased Prkce mRNA and both Sp1 sites methylated). |
Bisulfite sequencing/methylation analysis of Prkce promoter CpGs, luciferase reporter gene assay, electrophoretic mobility shift/SP1 binding assays, RT-PCR, in vivo rat model |
Biology of reproduction |
High |
18945988
|
| 2022 |
Maternal Prkce transcript in mature oocytes is critical for the first cleavage and facilitating the maternal-to-zygotic transition in mice. Prkce knockout mice showed a significantly reduced 2-cell rate (32.4% vs 80.1% in wild-type) that was rescued by Prkce cRNA injection (76.7% 2-cell rate). Global transcriptional analysis of knockout embryos revealed 143 differentially expressed genes largely enriched in cell cycle regulation pathways. |
Prkce knockout mice, in vitro fertilization, cRNA rescue injection, microarray/RNA sequencing, RT-qPCR, Western blotting, immunofluorescence |
Cell proliferation |
High |
35582855
|
| 2015 |
IPS-1-mediated anticancer signaling via IRF3 and IRF7 downregulates PRKCE (along with BCL2 and BIRC3) as part of its anti-apoptotic gene suppression program. Stable knockdown of IPS-1, IRF3, or IRF7 in IFN-non-responsive cancer cells reduced anticancer activity and suppressed downregulation of PRKCE. |
IPS-1 ectopic expression, stable shRNA knockdown of IPS-1/IRF3/IRF7, gene expression analysis, apoptosis assays in cancer cell lines |
Cell death & disease |
Medium |
25950488
|
| 2025 |
PKCε deficiency in the central nervous system leads to cerebral and cerebellar atrophy and motor/social deficits. Mechanistically, deletion of PKCε results in downregulation of VEGF/PI3K-induced AKT activation, causing abnormal brain development. This is consistent with the SHORT syndrome phenotype previously linked to PRKCE mutation. |
Prkce knockout mice (CNS-specific), brain morphometry, behavioral testing, phospho-specific immunoblotting of AKT pathway components |
Neuroscience bulletin |
Medium |
40914752
|
| 2025 |
A PRKCE::ETV6 fusion gene resulting from a complex chromosomal rearrangement of chromosomes 2 and 12 in near-ETP T-ALL confers interleukin-independent proliferation and enhanced survival in cytokine-dependent cellular models (Ba/F3 pro-B cells and D1 T-cells), supporting its role as an oncogenic driver. |
Targeted genomic capture high-throughput sequencing, RNA sequencing, RT-PCR, Sanger sequencing, FISH, ectopic expression of PRKCE::ETV6 fusion in Ba/F3 and D1 cell lines, IL-independent proliferation and survival assays |
Molecular and cellular pediatrics |
Medium |
41123786
|
| 2025 |
In bladder cancer cells, decreased PRKCE expression (associated with the rs4953292 A allele combined with 4-aminobiphenyl treatment) upregulates PKG and promotes phosphorylation of VASP within the cGMP-PKG signaling pathway, enhancing glucose uptake, lactate generation, and extracellular acidification rate to reprogram glycolysis, thereby promoting bladder cancer susceptibility. |
Functional experiments in 4-ABP-treated bladder cancer cells, allele-specific PRKCE expression analysis, ECAR measurement, lactate/glucose uptake assays, phospho-VASP immunoblotting |
Environment & health |
Medium |
41883368
|
| 2024 |
PRKCE protein associates with ribosomal complexes specifically in subcerebral projection neurons (SCPN) but not callosal projection neurons (CPN) during axonal connectivity establishment in mouse cortex. This SCPN-specific ribosome association was validated by ribosome immunoprecipitation and PKCε has enriched gene expression in SCPN, suggesting a role in subtype-specific translational regulation during circuit formation. |
Retrograde neuronal labeling, FACS purification of neuron subtypes, ribosome immunoprecipitation, ultra-low-input mass spectrometry, gene expression analysis |
bioRxivpreprint |
Low |
|
| 2024 |
Myeloid PKCε restricts lipid uptake in macrophages by a mechanism independent of scavenger receptor expression. PKCε-deficient macrophages (mεKO) retained significantly more cholesterol and lipid droplets upon lipid loading in vitro and in vivo, and RNA sequencing implicated higher expression of genes related to endocytosis in mεKO macrophages. mεKO mice developed larger atherosclerotic plaques with more necrosis and thinner collagen caps. |
Myeloid-specific Prkce knockout mice (LysM Cre PKCε fl/fl), bone marrow-derived macrophage lipid loading assays, cholesterol retention assays, RNA sequencing, in vivo hypercholesterolemia model, plaque histomorphometry |
bioRxivpreprint |
Medium |
|