| 2014 |
BRCA2 associates with PCID2 (a TREX-2 subunit) in the cell; depletion of PCID2 (along with other TREX-2 subunits GANP and DSS1) causes genome instability as measured by γ-H2AX/53BP1 foci accumulation and comet assay, but does not induce R-loop accumulation (detected by EGFP-RNase H1 hybrid-binding domain and S9.6 antibody), placing TREX-2/PCID2 in a pathway that prevents DNA damage independently of R-loop suppression. |
Co-immunoprecipitation (BRCA2-PCID2 association); siRNA depletion with γ-H2AX/53BP1 foci and single-cell electrophoresis; R-loop detection by EGFP-RNase H1 and S9.6 antibody |
Nature |
High |
24896180
|
| 2017 |
Pcid2 interacts with ZNHIT1 in multipotent progenitors to block SRCAP chromatin remodelling activity, thereby preventing deposition of histone variant H2A.Z and transcription factor PU.1 at key lymphoid fate regulator genes, and restricting lymphoid lineage commitment; Pcid2 deletion causes skewed lymphoid lineage specification. |
Co-immunoprecipitation (Pcid2-ZNHIT1 interaction); conditional Pcid2 knockout in haematopoietic system; H2A.Z and PU.1 chromatin localization assays; Znhit1 deletion epistasis |
Nature Communications |
High |
29138493
|
| 2014 |
Pcid2 is present in the CBP/p300-EID1 complex in embryonic stem cells. Pcid2 binds EID1 to impede its association with MDM2 (an E3 ligase that mediates K48-linked ubiquitination and proteasomal degradation of EID1), thereby stabilizing EID1 and sustaining its inhibition of CBP/p300 HAT activity, leading to suppression of developmental gene expression and maintenance of pluripotency. |
Co-immunoprecipitation (Pcid2-EID1, Pcid2-CBP/p300-EID1 complex); siRNA/knockdown; ubiquitination assays; Pcid2 knockout causing embryonic lethality before blastocyst stage |
Stem Cells |
High |
24167073
|
| 2010 |
Pcid2 selectively regulates MAD2 mRNA export; siRNA knockdown of Pcid2 reduces MAD2 protein expression (but not MAD1, BUBR1, cyclin A, cyclin B1, or CDK1), causing cell-cycle abnormalities (polyploidy) and increased apoptosis phenocopying MAD2 knockdown. Cd19-cre conditional deletion of Pcid2 causes mature B cell deficiency. |
siRNA knockdown with real-time RT-PCR and in situ RNA hybridization for MAD2 mRNA; flow cytometry for cell cycle/apoptosis; conditional knockout (Cd19-cre) |
Journal of Immunology |
Medium |
20870947
|
| 2021 |
Drosophila PCID2 is present in the cytoplasm and directly interacts with NudC protein, which maintains PCID2 cytoplasmic stability. Cytoplasmic PCID2 associates with mRNA and microtubules. PCID2 knockdown blocks nuclear mRNA export and also impairs general cytoplasmic mRNA transport, indicating a dual role in nuclear export and subsequent cytoplasmic mRNA trafficking. |
Subcellular fractionation/immunofluorescence for cytoplasmic localization; co-immunoprecipitation (PCID2-NudC); RNA immunoprecipitation (mRNA association); co-localization with microtubules; siRNA knockdown with mRNA localization assays |
RNA Biology |
Medium |
33602059
|
| 2013 |
Human PCID2 localizes to the centrosome in a subset of HeLa cells throughout the cell cycle, and this centrosomal localization is dependent on centrin 2. PCID2 (but not ENY2) is involved in nuclear protein export: siRNA knockdown of PCID2 delays (but does not block) nuclear protein export. Co-depletion of centrin 2 and PCID2 blocks rather than delays nuclear protein export. |
Immunofluorescence co-staining with centrosome markers and cyclins; siRNA knockdown; nuclear protein export assay; epistasis by co-depletion |
Experimental Cell Research |
Medium |
24291146
|
| 2021 |
PCID2 binds PML (promyelocytic leukemia protein, a tumor suppressor) as shown by co-immunoprecipitation and mass spectrometry. PCID2 promotes poly-ubiquitination and degradation of PML, which in turn activates canonical Wnt/β-catenin signaling and represses the ARF-p53 pathway in colorectal cancer cells. |
Co-immunoprecipitation and mass spectrometry; ubiquitination assay; gain/loss-of-function in cell lines and xenograft mouse models; Western blotting for pathway activation |
Oncogene |
Medium |
34625711
|
| 2024 |
PCID2 binds the latent HIV-1 LTR promoter and represses transcription initiation. PCID2 depletion remodels the chromatin landscape at the HIV-1 promoter and causes latency reversal. Immunoprecipitation-mass spectrometry identified PCID2-interacting proteins as negative viral RNA splicing regulators; PCID2 depletion leads to over-splicing of intron-containing viral RNA. PCID2 acts within a TREX2 sub-complex (PCID2-DSS1-MCM3AP) to block transcription and dysregulate viral RNA processing. |
ChIP (PCID2 at HIV-1 LTR); siRNA depletion with chromatin remodeling analysis; IP-mass spectrometry; viral RNA splicing assays; latency reversal assays in cell lines and primary cells from people with HIV |
iScience |
Medium |
38384833
|
| 2023 |
The C-terminal region of the WH domain of Drosophila PCID2 specifically binds the 3′-noncoding region of ras2 RNA (shown by EMSA). An additional RNA-binding region (M region) in the N-terminal part of the PCI domain binds RNA nonspecifically. Point mutations of conserved residues in the M region abolish PCID2-RNA interaction; deletion of the C-terminal domain only partly decreases it, indicating both regions are required for full RNA binding. |
Electrophoretic mobility shift assay (EMSA); deletion and point mutagenesis of PCID2 domains |
Current Issues in Molecular Biology |
Medium |
37504273
|
| 2023 |
Deletion of the C-terminal sequence of Drosophila PCID2 decreases its interaction with RNA and impairs mRNA export from the nucleus to the cytoplasm in D. melanogaster cells. |
PCID2 C-terminal deletion constructs; mRNA export assays in D. melanogaster cells |
Doklady Biochemistry and Biophysics |
Low |
38066318
|
| 2024 |
Point mutations of conserved amino acids in the M region of Drosophila PCID2 disrupt its interaction with cellular RNAs and cause defective export of polyA-containing mRNAs from the nucleus to the cytoplasm in Drosophila cells. |
Point mutagenesis in M domain; RNA-binding assays; polyA mRNA export assays in Drosophila cells |
Doklady Biological Sciences |
Low |
39128950
|
| 2025 |
The M-PCID2 and C-PCID2 RNA-binding regions of Drosophila PCID2 competitively bind ras2 fr4_2 mRNA, with M-PCID2 binding more efficiently and displacing C-PCID2. Point mutations in M-PCID2 that disrupt full-length PCID2-RNA interaction paradoxically increase M-PCID2 fragment affinity for RNA, suggesting that additional factors are required to transition from nonspecific to specific binding in the intact complex. |
EMSA with isolated M-PCID2 and C-PCID2 fragments and point mutants; competition binding assays |
Doklady Biochemistry and Biophysics |
Low |
41083631
|
| 2025 |
The N-terminal region of Drosophila PCID2 interacts with its C-terminal (C-PCID2) region via distinct surfaces that do not overlap with the RNA-binding surface of C-PCID2, indicating an intramolecular interaction that may modulate TREX-2 function without blocking RNA binding. |
In vitro protein interaction assays between isolated PCID2 domain fragments |
Doklady Biochemistry and Biophysics |
Low |
41083629
|
| 2015 |
Molecular dynamics simulations of PCID2 in complex with the intrinsically disordered protein DSS1 show that DSS1 binding reduces conformational variation of PCID2 (particularly helices IV and VIII), promotes coil formation between helix III and IV, and induces a short anti-parallel β-sheet. Decomposition of binding free energy indicates electrostatic and hydrophobic interactions (including a seven-residue hydrophobic core in DSS1) are key for DSS1-PCID2 recognition. |
Molecular dynamics simulation (3 × 500 ns); binding free energy decomposition |
Journal of Molecular Modeling |
Low |
25914122
|
| 2026 |
PCID2 acts as a scaffold for mutually exclusive SAC3(PCI-fold)-based subcomplexes with GANP, LENG8, and SAC3D1 within the TREX2 system. The GANP-PCID2-SEM1 subcomplex localizes at the nuclear envelope and mediates canonical mRNA export, while the LENG8-PCID2-SEM1 subcomplex localizes to nuclear speckles and interacts with mRNA processing factors to influence polyadenylation site usage. The two SAC3-containing subcomplexes have distinct and alternative localizations and functions. |
Interactome mapping (IP-MS); depletion experiments with RNA-seq; subcellular localization by immunofluorescence; transcriptomic analysis of polyadenylation site usage |
bioRxivpreprint |
Medium |
42039562
|
| 2025 |
LENG8 binds PCID2 and SEM1 to form the REX (Repressor of EXport) complex, which acts as a dominant negative factor for TREX-2-mediated mRNA export and causes nuclear RNA retention. The LENG8-PCID2-SEM1 trimer is structurally and functionally equivalent to the GANP-PCID2-SEM1 trimer of TREX-2. LENG8 depletion leads to leakage of misprocessed mRNAs and noncoding RNAs into the cytoplasm; LENG8 also promotes RNA degradation by recruiting PAXT and the nuclear RNA exosome. |
Co-immunoprecipitation (LENG8-PCID2-SEM1 complex); structural analysis; siRNA depletion with RNA-seq; mRNA export/retention assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.08.14.670437
|
| 2025 |
The LENG8-PCID2-SEM1 (LENG8-PS) trimer is structurally and functionally equivalent to the central GANP-PCID2-SEM1 (GANP-PS) trimer of TREX-2. The LENG8-PS module is part of the PAXT connection and releases polyadenylated RNAs from UAP56 for nuclear exosome-mediated decay, while the NPC-associated TREX-2 (GANP-PS) releases RNAs for export. Mutagenesis and transcriptomic data show that competing actions of PAXT (with LENG8-PS) and TREX-2 (with GANP-PS) govern nuclear fate of polyadenylated RNPs. |
Structural analysis; mutagenesis; transcriptomics; biochemical reconstitution of competing complexes |
bioRxivpreprint |
Medium |
bio_10.1101_2025.09.16.676470
|
| 2026 |
PCID2 is required for spermatogonial differentiation; conditional knockout (Stra8-Cre) causes male infertility, germ cell apoptosis, developmental arrest at type A to type B spermatogonia transition, and failure of meiosis initiation. IP-MS and co-IP show PCID2 interacts with splicing factors SNRPG, hnRNPH1, and SF3B1 in germ cells to modulate alternative splicing of Prpf3, Nek3, Dvl2, and Slc30a9. |
Conditional knockout (Stra8-Cre); single-cell transcriptomics; IP-MS and co-IP; RNA-seq with splice analysis; RT-PCR validation |
Cellular and Molecular Life Sciences |
High |
41526677
|