| 2014 |
ZDHHC1 is an ER-associated protein that constitutively associates with MITA/STING and mediates dimerization/aggregation of MITA/STING as well as recruitment of downstream signaling components TBK1 and IRF3, acting as a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling. Zdhhc1-knockout cells failed to produce IFNs and cytokines in response to DNA (but not RNA) viruses. |
Expression screen for IFNB1 promoter activation, Zdhhc1 knockout cells and mice, co-immunoprecipitation, cytokine measurement, HSV-1 infection model |
Cell host & microbe |
High |
25299331
|
| 2013 |
ZDHHC1 (zDHHC1/z1, DHHC1) acts as a palmitoylating enzyme for neurochondrin (Ncdn), palmitoylating it at Cys-3 and Cys-4, and this palmitoylation is required for targeting Ncdn to Rab5-positive early endosomes. ZDHHC1 itself co-localizes with Rab5-positive endosomes, and knockdown of DHHC1 causes loss of Ncdn from these endosomes. |
In silico substrate prediction, DHHC enzyme library screening, palmitoylation assay, STED microscopy, siRNA knockdown, subcellular localization by fluorescence imaging |
The Journal of biological chemistry |
Medium |
23687301
|
| 2017 |
In teleost (grass carp), ZDHHC1 and STING each interact directly with IRF3 (demonstrated by co-immunoprecipitation and GST pull-down), promote IRF3 dimerization and nuclear translocation, and activate IFN-β expression. STING knockdown inhibits IFN expression and ZDHHC1-mediated IFN activation, indicating STING is required upstream of ZDHHC1 in this pathway. ZDHHC1 knockdown inhibits IFN expression but does not affect STING levels. |
Co-immunoprecipitation, GST pull-down, siRNA knockdown, IFN promoter reporter assay, overexpression in Ctenopharyngodon idella kidney cells |
Journal of immunology |
Medium |
29046345
|
| 2020 |
ZDHHC1 is transcriptionally upregulated by p53, and the resulting ZDHHC1 protein interacts with IFITM3 to promote its S-palmitoylation and protein stability, thereby inhibiting Japanese encephalitis virus (JEV) replication. Knockdown of IFITM3 impaired the anti-JEV effect of ZDHHC1, and knockdown of either ZDHHC1 or IFITM3 compromised p53-mediated anti-JEV activity. JEV reduces p53 expression to impair ZDHHC1-mediated IFITM3 palmitoylation as a viral evasion mechanism. |
Palmitoyltransferase screening, siRNA knockdown, Co-IP, palmitoylation assay, viral replication assay, protein stability assay |
PLoS pathogens |
Medium |
33108395
|
| 2021 |
ZDHHC1 acts as an S-palmitoyltransferase that palmitoylates p53 at Cys-135, Cys-176, and Cys-275. This palmitoylation is required for nuclear translocation of p53. In a feedback loop, p53 recruits DNMT3A to the ZDHHC1 promoter, causing hypermethylation and silencing of ZDHHC1, thereby limiting its own nuclear import. |
Palmitoylation assay with site-directed mutagenesis (C135, C176, C275), nuclear translocation assay, chromatin immunoprecipitation, methylation analysis |
Oncogene |
Medium |
34282274
|
| 2020 |
Restoration of ZDHHC1 expression in cancer cells inhibits glucose metabolism in a CYGB-dependent manner, suppresses the pentose phosphate pathway, and induces oxidative stress and ER stress leading to pyroptosis and apoptosis. Proteomic and metabolomic analyses identified these pathway alterations as ZDHHC1-dependent. |
iTRAQ proteomics, GC-MS metabolomics, Western blot, oxidative/ER stress indicator assays, xenograft mouse model, indirect immunofluorescence |
Theranostics |
Medium |
32863941
|
| 2024 |
ZDHHC1 palmitoylates IGF2BP1 at Cys-337; this S-palmitoylation results in downregulation of LIPG mRNA stability via m6A modification, inhibiting CRC cell proliferation and invasion. The ZDHHC1/IGF2BP1/LIPG signaling axis was defined by functional rescue and mechanistic experiments. |
Palmitoylation assay with site mutagenesis (C337), Co-IP, m6A modification analysis, in vitro and in vivo cell growth assays |
Cancer gene therapy |
Medium |
39069526
|
| 2024 |
ZDHHC1 palmitoylates p110α (the catalytic subunit of PI3K) in macrophages; loss of Zdhhc1 reduces p110α palmitoylation, promotes nuclear translocation of p110α, and significantly decreases downstream phosphorylation of Akt (Ser473) and mTOR (Ser2448), thereby reducing foam cell formation and atherosclerotic plaque development. |
Zdhhc1 knockout in THP-1 cells and ApoE−/− mice, mass spectrometry palmitoylation analysis, bioinformatic pathway analysis, Western blot for PI3K-Akt-mTOR phosphorylation, nuclear fractionation, ox-LDL uptake assay |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
39566590
|
| 2024 |
Zdhhc1 and Zdhhc2 co-operatively palmitoylate Gpm6a at Cys17, Cys18, and Cys246, which is required for lipid raft formation mediated by Gpm6a, thereby stabilizing Procr protein and maintaining mammary stem cell (aMaSC) activity and postnatal mammary development. |
Gpm6a knockout mouse model, Zdhhc1/2 palmitoylation assay with site mutagenesis, lipid raft fractionation, Procr protein stability assay, mammary reconstitution assay |
Cell reports |
Medium |
39321020
|
| 2025 |
ZDHHC1 physically interacts with GSDMD (gasdermin D) and mediates its palmitoylation; ZDHHC1 overexpression enhances GSDMD palmitoylation-mediated membrane translocation and pyroptosis in prostate cancer cells, and this effect is partially reversed by the palmitoylation inhibitor 2-BP. |
Co-IP, palmitoylation assay, 2-BP palmitoylation inhibitor, GSDMD membrane translocation assay, pyroptosis markers (IL-1β, IL-18, LDH, HMGB1), in vivo xenograft model |
Naunyn-Schmiedeberg's archives of pharmacology |
Medium |
40237800
|
| 2022 |
In Chinese perch (Siniperca chuatsi), ZDHHC1 interacts with MITA (the fish ortholog of STING) by co-immunoprecipitation, and overexpression of ZDHHC1 upregulates ISGs (Mx, RSAD2, IRF3) and type I IFNs, consistent with an antiviral adaptor role conserved from fish to mammals. |
Co-immunoprecipitation, overexpression, qRT-PCR for ISG/IFN expression, in vivo infection with ISKNV |
Fish & shellfish immunology |
Low |
36122636
|