pdzrn3 is required for pronephros morphogenesis in Xenopus laevis

Marracci, Silvia; Vangelisti, Alberto; Raffa, Vittoria; Andreazzoli, Massimiliano; Dente, Luciana

doi:10.1387/ijdb.150381ld

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…We established PDZRN3 as a possible EMX2 target in cervical cancer. The morphogenesis regulator PDZRN3 and its family members are involved in cell differentiation [ 58 , 60 , 61 ]. Furthermore, in cervical cancer, HPV-18 E6-induced PDZRN3 degradation can lead to an increase in STAT5 activation [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Jiang

Shi

2022

Journal of Healthcare Engineering

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The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.

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Section: Discussionmentioning

confidence: 99%

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Jiang

Shi

2022

Journal of Healthcare Engineering

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“…The latter can promote the modification of the ubiquitination process of related molecules via the E3 ubiquitin ligase domain. This phenomenon is mediated by the decrease in Muscle-Specific Kinase expression via PDZRN3-induced ubiquitination (17,18). PDZRN3 interacts with the E3 ubiquitin ligase domain.…”

Section: Introductionmentioning

confidence: 99%

Lower expression of PDZRN3 induces endometrial carcinoma progression via the activation of canonical Wnt signaling

Li¹,

Zhong²,

Yang

et al. 2022

Oncol Lett

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Endometrial carcinoma (EC) exhibits an extremely malignant biological behavior and has a high mortality rate. EC has recently become one of the most lethal cancers in women worldwide. E3 ubiquitin ligases play an important role in the biological function of healthy cells but can also contribute to tumorigenesis and cancer development. PDZ Domain Containing Ring Finger 3 (PDZRN3) is associated with cell differentiation and its structure includes the E3 ubiquitin ligase. However, the effects of PDZRN3 in EC remain unclear. Reverse transcription-quantitative PCR was used to detect the expression levels of PDZRN3 in EC cells, and the role of PDZRN3 in EC progression was determined using western blotting, MTT, colony formation, Transwell, subcutaneous tumor formation and pulmonary metastasis assays. A multi-pathway reporter arrays and western blotting were performed to investigate the potential biological mechanisms of PDZRN3 in EC. The present study demonstrated that PDZRN3 served an essential role in metastasis and proliferation of EC. PDZRN3 expression was lower in EC tissues compared with that in normal endometrial tissues. Low expression level of PDZRN3 in EC was correlated with certain clinicopathological features of patients with EC, such as the age of the patients, the tumor grade and the tumor subtype. The invasive and proliferative activities of EC cells with low expression of PDZRN3 were more potent than those of EC cells with high expression of PDZRN3, which was confirmed by in vivo and in vitro experiments. Furthermore, lower expression of PDZRN3 promoted metastasis and proliferation via activation of the canonical Wnt signaling pathway. The present study demonstrated that decreased PDZRN3 expression promoted metastasis and proliferation in EC cells via activation of the canonical Wnt signaling pathway, highlighting a potential biological therapeutic target for the management of EC.

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“…A member of PDZ domain containing RING finger (PDZRN) includes a RING finger domain at an amino terminus and two or four PDZ domains at the carboxyl terminus. PDZRN3 has been reported to play positive roles in the myoblast differentiation (18) and nephrogenesis in Xenopus laevis (19). In contrast, it has negative roles in the bone morphogenetic protein-2-induced osteoblast differentiation (20) and adipogenesis in mouse 3T3-L1 preadipocytes (21).…”

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confidence: 99%

The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the Mg2+ regulator claudin-16 in renal tube epithelial cells

Marunaka

Furukawa

Fujii

et al. 2017

Journal of Biological Chemistry

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Ion exchange in the renal tubules is fundamental to the maintenance of physiological ion levels. Claudin-16 (CLDN16) regulates the paracellular reabsorption of Mg in the thick ascending limb of Henle's loop in the kidney, with dephosphorylation of CLDN16 increasing its intracellular distribution and decreasing paracellular Mg permeability. CLDN16 is located in the tight junctions, but the mechanism regulating its localization is unclear. Using yeast two-hybrid systems, we found that CLDN16 binds to PDZRN3, a protein containing both RING-finger and PDZ domains. We also observed that the carboxyl terminus of the cytoplasmic CLDN16 region was required for PDZRN3 binding. PZDRN3 was mainly distributed in the cytosol of rat kidney cells and upon cell treatment with the protein kinase A inhibitor H-89, colocalized with CLDN16. H-89 also increased mono-ubiquitination and the association of CLDN16 with PDZRN3. Mono-ubiquitination levels of a K275A mutant were lower, and its association with PDZRN3 was reduced compared with wild-type (WT) CLDN16 and a K261A mutant, indicating that Lys-275 is the major ubiquitination site. An S217A mutant, a dephosphorylated form of CLDN16, localized to the cytosol along with PDZRN3 and the endosomal marker Rab7. PDZRN3 siRNA increased cell-surface localization of WT CLDN16 in H-89-treated cells or containing the S217A mutant and also suppressed CLDN16 endocytosis. Of note, H-89 decreased paracellular Mg flux in WT CLDN16 cells, and PDZRN3 siRNA increased Mg flux in the H-89-treated WT CLDN16 and S217A mutant cells. These results suggest that PDZRN3 mediates endocytosis of dephosphorylated CLDN16 and represents an important component of the CLDN16-trafficking machinery in the kidney.

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pdzrn3 is required for pronephros morphogenesis in Xenopus laevis

Cited by 4 publications

References 27 publications

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Lower expression of PDZRN3 induces endometrial carcinoma progression via the activation of canonical Wnt signaling

The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the Mg2+ regulator claudin-16 in renal tube epithelial cells

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