| 1998 |
P52rIPK (THAP12/PRKRIR) was identified as a novel P58IPK-interacting protein that inhibits P58IPK function, thereby restoring PKR activity and eIF-2alpha phosphorylation. P52rIPK and P58IPK interacted in yeast two-hybrid assays and were recovered as a complex from mammalian cell extracts. In a reconstituted in vitro PKR-regulatory assay, P52rIPK inhibited P58IPK function, resulting in upregulation of PKR-mediated eIF-2alpha phosphorylation and growth suppression. |
Interaction cloning, yeast two-hybrid, co-immunoprecipitation from mammalian cells, reconstituted in vitro PKR-regulatory assay, yeast growth suppression assay |
Molecular and cellular biology |
High |
9447982
|
| 2002 |
The 114 amino acid charged domain of P52rIPK (THAP12) is necessary and sufficient for interaction with P58IPK, binding specifically to P58IPK TPR domain 7 (adjacent to the TPR motif required for PKR interaction). Both the P52rIPK charged domain and P58IPK TPR7 were required for downstream control of PKR activity, eIF-2alpha phosphorylation, and cell growth. P52rIPK and P58IPK formed a stable intracellular complex during the acute response to cytoplasmic stress induced by various stimuli. |
Domain deletion/mutagenesis, in vitro binding assays, cell growth assays, PKR activity and eIF-2alpha phosphorylation assays, co-immunoprecipitation under stress conditions |
Biochemistry |
High |
12269832
|
| 2002 |
DAP4 (THAP12/PRKRIR) is a constitutively nuclear polypeptide that homodimerizes through its amino terminus and binds MST1 kinase through its carboxyl-terminal segment. Coexpression of DAP4 with submaximal MST1 enhances MST1-induced apoptosis in a dose-dependent fashion. DAP4 is not significantly phosphorylated by MST1 and does not alter MST1 kinase activity in vitro, but DAP4 binds endogenous and recombinant p53, potentially enabling colocalization of MST1 with p53. |
Co-immunoprecipitation in COS-7 cells, leptomycin B nuclear accumulation assay, co-expression apoptosis assay, in vitro kinase assay, p53 binding assay with recombinant proteins |
The Journal of biological chemistry |
High |
12384512
|
| 2005 |
THAP0 (an alias for DAP4/THAP12) was identified as a member of the THAP protein family defined by a zinc-dependent sequence-specific DNA-binding THAP domain containing a C2CH signature. The THAP domain of THAP1 (a related family member) was demonstrated to be a zinc-dependent DNA-binding domain; by implication THAP0/THAP12 shares this domain architecture, qualifying it as a nuclear proapoptotic factor within this family. |
Phylogenetic/domain analysis; biochemical characterization of THAP domain zinc-dependence and DNA binding via zinc chelation (1,10-o-phenanthroline), site-directed mutagenesis of C2CH residues, in vitro binding-site selection (THAP1 as representative domain) |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
15863623
|
| 2011 |
PRKRIR (THAP12) was identified as a novel RIG-I interacting protein. The C-terminal domain of PRKRIR is required for physical interaction with RIG-I and for signal augmentation. PRKRIR blocks poly-ubiquitination and proteasomal degradation of RIG-I, thereby increasing cellular RIG-I protein levels and synergistically enhancing type I IFN production mediated by signal-activated or constitutively active RIG-I. Overexpression of PRKRIR together with active RIG-I efficiently inhibits virus replication. |
Co-immunoprecipitation in HEK293FT cells, domain deletion mapping (C-terminal domain), ubiquitination assay, IFN reporter assay, virus replication assay |
Biochemical and biophysical research communications |
Medium |
21910972
|
| 2024 |
THAP12 interacts with ZFP574 (a zinc finger protein) to form a nuclear complex that promotes the G1-to-S phase transition during cell cycle progression. Mutation of ZFP574 impairs nuclear localization of the ZFP574-THAP12 complex. THAP12 deficiency results in cell cycle arrest and impaired lymphoproliferation. In a Myc-driven B cell leukemia mouse model, disruption of ZFP574-THAP12 complex suppressed malignant B cell growth while largely sparing normal B cells. |
Forward genetic screen in mice, co-immunoprecipitation (ZFP574-THAP12 interaction), nuclear localization imaging, cell cycle analysis, conditional/acute gene deletion, targeted protein degradation, in vivo leukemia suppression model |
Proceedings of the National Academy of Sciences of the United States of America |
High |
39047044
|
| 2026 |
Biallelic loss-of-function variants in THAP12 cause severe developmental and epileptic encephalopathy. Patient-derived compound heterozygous variants reduce THAP12 protein abundance. In mouse models, homozygous or compound heterozygous Thap12 mutations cause embryonic lethality, confirming an essential dosage-sensitive role in early development. Zebrafish thap12 loss-of-function models exhibit microcephaly, brain hypoplasia, abnormal neuronal activity, and increased seizure sensitivity; transcriptomic profiling revealed dysregulation of cell cycle and apoptotic pathways with increased cell death and reduced proliferation. Wild-type human THAP12 mRNA rescued these zebrafish phenotypes, whereas patient-variant alleles failed to rescue. |
Whole-genome sequencing of patients, mouse genetic models (homozygous and compound heterozygous), zebrafish loss-of-function models, mRNA rescue experiments with wild-type vs. patient variants, transcriptomic profiling of larval zebrafish brains, cell death/proliferation assays |
medRxivpreprint |
Medium |
41822681
|
| 2026 |
THAP12 interacts with LDOC1 in the nucleus of NSCLC cells. THAP12 overexpression increased LDOC1 recovery in nuclear histone fractions. LDOC1 knockdown-induced loss of chromatin-bound H2Bub1 and enhanced chromatin compaction were partially mediated by the LDOC1-THAP12 interaction, placing THAP12 within an epigenetic regulatory axis controlling histone H2B monoubiquitination and chromatin accessibility. |
Co-immunoprecipitation, proximity ligation assay, nuclear fractionation, ChIP-seq, ATAC-seq, MNase digestion assay with THAP12 overexpression |
Cell communication and signaling : CCS |
Medium |
41484780
|