| 2013 |
PBF/PTTG1IP is a tyrosine phosphoprotein that specifically binds the proto-oncogene tyrosine kinase Src (identified by mass spectrometry, GST pulldown, and co-immunoprecipitation). Src-mediated phosphorylation occurs at PBF residue Y174; abrogation of Y174 results in plasma membrane retention of PBF and markedly reduced ability to bind and internalize NIS (sodium iodide symporter), thereby increasing radioiodide uptake. The Src inhibitor PP1 inhibits PBF phosphorylation and restores iodide uptake in thyroid cells. |
Mass spectrometry, GST pulldown, co-immunoprecipitation, site-directed mutagenesis (Y174 substitution), radioiodide uptake assays in TPC1 cells and human primary thyroid cells, Src inhibitor (PP1) treatment |
The Journal of clinical endocrinology and metabolism |
High |
23678037
|
| 2014 |
PBF/PTTG1IP binds specifically to p53 in thyroid cells (shown by co-immunoprecipitation and proximity-ligation assay) and represses p53 transactivation of responsive promoters. PBF decreases p53 protein stability by enhancing its ubiquitination, an effect dependent on the E3 ligase activity of Mdm2. In transgenic PBF-overexpressing mouse thyroids, impaired p53 function was associated with significantly increased genomic instability and repression of ~40% of DNA repair genes. |
Co-immunoprecipitation, proximity-ligation assay, p53 transactivation reporter assays, ubiquitination assays, transgenic mouse model with thyroid-specific PBF overexpression, fluorescent ISSR-PCR for genomic instability, gene expression analysis of DNA repair genes |
Endocrinology |
High |
24506068
|
| 2011 |
Transgenic thyroid-specific overexpression of PBF/PTTG1IP in mice causes thyroid gland enlargement with hyperplastic and macrofollicular lesions, upregulation of Akt, TSH receptor, and cyclin D1, and potent repression of sodium iodide symporter (NIS) expression and iodide uptake. PBF depletion in primary thyroid cultures rescued iodide uptake, establishing PBF as a direct repressor of NIS-mediated radioiodide uptake. |
Transgenic mouse model (thyroid-specific PBF overexpression), primary thyroid culture iodide uptake assays, PBF siRNA depletion, western blotting/IHC for Akt, TSHR, cyclin D1, NIS |
Cancer research |
High |
21844185
|
| 2017 |
Missense mutations C51R and R140W in PBF/PTTG1IP reduce protein stability (assessed by anisomycin half-life studies), restrict subcellular localization to the ER (C51R) or Golgi (R140W) rather than the plasma membrane, abolish the capacity to induce cellular migration and invasion, and eliminate colony formation and anchorage-independent growth. However, both mutants retain the ability to repress radioiodide uptake. Wild-type PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice. |
Anisomycin half-life/stability assays, subcellular localization imaging, migration and invasion assays, colony formation and soft agar assays, radioiodide uptake assays |
Endocrine-related cancer |
Medium |
28676500
|
| 2024 |
PTTG1IP is a small, N-glycosylated single-spanning transmembrane protein that is naturally sorted into extracellular vesicles (EVs). Its EV loading is dependent on N-glycosylation at two arginine residues. When used as a scaffold for chimeric fusion proteins (PTTG1IP fused to cargo via self-cleaving sequences), it enables highly efficient functional delivery of Cre recombinase and Cas9-sgRNA complexes to recipient cells and mouse xenograft tumors. |
Bioinformatics analysis of N-glycosylation as EV-sorting feature, mutagenesis of N-glycosylation sites, EV loading assays, functional delivery assays (Cre reporter, Cas9-sgRNA reporter) in cell culture and mouse xenograft |
Extracellular vesicle |
Medium |
39712388
|
| 2022 |
The transcription factor Sp4 binds to Sp4 response elements in the PTTG1IP promoter region (−212 to +7 bp) and drives PTTG1IP gene transcription and expression; overexpression of Sp4 increased PTTG1IP mRNA and protein levels in HeLa cells. |
Luciferase reporter assay (5' flanking region deletion constructs), electrophoretic mobility shift assay (EMSA), Sp4 overexpression in HeLa cells |
DNA and cell biology |
Medium |
36383136
|
| 2025 |
PTTG1IP forms an endogenous complex with cortactin (CTTN) in thyroid cancer cells, as shown by co-immunoprecipitation and co-localization by immunofluorescence. Additionally, ChIP-qPCR demonstrated that PTTG1IP occupies the promoters of DDR genes BRCA1, BRCA2, RAD51, RAD51AP1, and ATM. Depletion of PTTG1IP increased radiation-induced DNA damage and cell death, establishing a role in DNA damage response. |
Co-immunoprecipitation, immunofluorescence co-localization, ChIP-qPCR, shRNA knockdown, γH2AX immunofluorescence, cell viability and apoptosis assays after irradiation |
Frontiers in bioscience (Landmark edition) |
Medium |
41074439
|
| 2012 |
A VNTR polymorphism in the PTTG1IP promoter is functional: increasing the number of tandem repeats enhances the binding affinity of estrogen receptor α (ERα) to the promoter, as shown by functional analysis, linking ERα-mediated transcriptional regulation of PTTG1IP to breast cancer risk. |
Genotyping of VNTR polymorphism, functional ERα binding affinity analysis (reporter/binding assay) |
Cancer science |
Low |
22404099
|