| 2006 |
NMR solution structure of PPIL1 was determined, revealing a cyclophilin-family fold with PPIase activity. GST pulldown and surface plasmon resonance experiments established that PPIL1 stably associates with the N-terminal region of SKIP (residues 59–129) with a dissociation constant of 1.25×10⁻⁷ M. Chemical shift perturbation NMR mapped the SKIP binding interface on PPIL1 to a site distinct from the PPIase active site. |
NMR structure determination, GST pulldown, surface plasmon resonance, chemical shift perturbation NMR |
The Journal of biological chemistry |
High |
16595688
|
| 2009 |
The N-terminal region of SKIP (residues 59–129) is intrinsically disordered; upon binding PPIL1 it undergoes a disorder-to-order transition. NMR structure of the PBF·PPIL1 complex showed that a minimal 21-residue SKIP fragment (residues 59–79) binds PPIL1 via electrostatic and hydrophobic interactions through a region distinct from the PPIase active site, leaving the active site open and available for isomerase/chaperone activity on other spliceosomal substrates. |
NMR structure determination of complex, NMR dynamics analysis of intrinsic disorder |
The Journal of biological chemistry |
High |
20007319
|
| 2010 |
Crystal structure of PPIL1 bound to the inhibitor cyclosporine A (CsA) was solved at 1.15 Å resolution (SAD phasing with Cd²⁺). A peptide array identified a minimal 36-residue linear epitope from SKIP (centred on an 8-residue core) sufficient to bind PPIL1 in pulldown assays. Molecular docking using the crystal structure and NMR data produced a model in which a SKIP proline is buried in a hydrophobic pocket of PPIL1, surrounded by hydrogen bonds, consistent with SKIP recruiting PPIL1 into the spliceosome core. |
X-ray crystallography (1.15 Å), peptide array, GST pulldown, molecular docking |
PloS one |
High |
20368803
|
| 2006 |
PPIL1 promotes colon cancer cell growth: siRNA knockdown of PPIL1 in SNUC4/SNUC5 cells retarded proliferation, and overexpression increased colony formation in NIH3T3 and HEK293 cells. Co-immunoprecipitation identified SNW1/SKIP and stathmin as PPIL1-interacting proteins. |
siRNA knockdown + growth assay, colony formation assay, co-immunoprecipitation |
Clinical cancer research |
Medium |
16397026
|
| 2001 |
Yeast two-hybrid screens in Dictyostelium discoideum and Schizosaccharomyces pombe identified cyclophilins (CypE/Cyp2) as the orthologues of human PPIL1; both bind their respective SNW/SKIP proteins at the N-terminal region of SNW in a cyclosporin A-independent manner, establishing the conserved PPIL1–SKIP interaction. CypE was confirmed in vitro to have cyclosporin A-sensitive PPIase activity. |
Yeast two-hybrid, in vitro PPIase activity assay |
Biochimica et biophysica acta |
Medium |
11690648
|
| 2020 |
Biallelic loss-of-function mutations in PPIL1 cause pontocerebellar hypoplasia with microcephaly (PCHM) in humans. PPIL1 patient-mutation knockin mice showed neuron-specific apoptosis. Loss of PPIL1 disrupted splicing integrity, predominantly affecting short and high-GC-content introns and genes linked to brain disorders. PPIL1 and PRP17 form an active isomerase–substrate interaction, but isomerase activity per se is not critical for PPIL1's spliceosomal function, establishing a non-enzymatic role for the prolyl isomerase. |
Patient genetics, PPIL1 knockin mouse model (neuronal apoptosis readout), splicing analysis (RNA-seq of affected introns), biochemical isomerase-activity mutagenesis |
Neuron |
High |
33220177
|
| 2004 |
PPIL1 is recruited by SKIP into the spliceosome as a foldase/prolyl isomerase, providing a mechanistic link between the SKIP transcriptional coregulator and spliceosome activation; PPIL1 is a component of the 35S U5 snRNP and the 45S activated spliceosome. |
Biochemical fractionation/spliceosome purification (review of primary data) |
Cellular and molecular life sciences : CMLS |
Low |
15052407
|
| 2022 |
Intracellular C3b-α'2 (generated downstream of S1PR1 activation) associates with PPIL1 via glutamic acid 156 (E156) and aspartic acid 111 (D111) of C3b-α'2, and this interaction is required for NLRP3/inflammasome induction and tumor metastasis; mutation of these C3b residues to prevent PPIL1 binding attenuated inflammasome activation and reduced lung colonization in mice. |
Site-directed mutagenesis of C3b, co-immunoprecipitation, in vivo lung colonization assay, NLRP3 inflammasome readout |
Cell reports |
Medium |
36476873
|
| 2025 |
NMR titration experiments showed that proline-rich PxxP motifs within the EWS low-complexity domain (EWSLCD) engage the catalytic face of PPIL1, forming low-affinity 'fuzzy' complexes. This interaction is absent when the RRM and RGG2 domains are included in the EWS construct, indicating that PxxP accessibility is context-dependent. PPIL1 is recruited into EWSLCD phase-separated condensates and alters their condensation properties at low salt concentrations. |
NMR titration, phase separation/droplet assay |
Biochemistry |
Medium |
40668764
|
| 2025 |
PPIL1 knockdown in HCC cell lines suppressed proliferation, migration, and sphere-forming capacity, and reduced tumor growth in xenograft mice. Transcriptome analysis after PPIL1 knockdown identified DAAM2 as a downstream transcriptional target, linking PPIL1 to Wnt/β-catenin signaling activation in liver cancer stem cells. |
shRNA knockdown, xenograft mouse model, sphere formation assay, transcriptome analysis |
Cancer genomics & proteomics |
Medium |
40883023
|