Paired Box 4 Proteins (PAX4)

Human Paired Box 4 (PAX4) interaction partners

1. Study identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes.

2. Viability of beta-cell was reduced under glucotoxic stress condition for the cells overexpressing either PAX4 R192H or PAX4 P321H or both. Thus these PAX4 polymorphisms may increase T2D risk by defective transcription regulation of target genes and/or decreased beta-cell survival in high glucose condition.

3. PAX4 IVS7-1G>A contributes to the pathogenesis of diabetes in this maturity-onset diabetes of the young, type 9 family through beta-cell dysfunction

4. The PAX4 variant rs6467136 was associated with the therapeutic effect of rosiglitazone in Chinese T2DM patients.

5. PAX4-miR (show MLXIP Proteins)-144/451-ADAMs axis regulates human epithelial cancer metastasis

6. These data suggest that acute PAX4 overexpression can reduce expression of aristaless related homeobox and glucagon (show GCG Proteins) during embryonic stem cell differentiation resulting in improved numbers of unihormonal insulin (show INS Proteins)-positive cells.

7. Tph1 (show TPH1 Proteins) and increased EC cell number occurred before the onset of obesity and hyperleptinemi. In addition, leptin (show LEP Proteins) deficiency was associated with reduced Pax4 mRNA, oral leptin (show LEP Proteins) treatment enhanced both Tph1 (show TPH1 Proteins) and Pax4 mRNA.

8. MAFA (show KLRG1 Proteins) nuclear expression in pancreatic alpha and beta cells, and the percentage of alpha cells expressing PAX4 are altered in patients with type 2 diabetes.

9. PAX4 R192H polymorphism generated a protein with defect in transcriptional repressor activities on its target genes, which may lead to beta-cell dysfunction associated with maturity onset diabetes of the young and early onset-age of type 2 diabetes.

10. A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative ketosis-prone diabetes in Chinese Han population.

Mouse (Murine) Paired Box 4 (PAX4) interaction partners

1. Down-regulation of PAX4 or its target gene encoding the p97/VCP (show vcp Proteins) ATPase reduced myofibril disassembly.

2. Ectopic expression of Pax4 in pancreatic delta cells results in beta-like cell neogenesis.

3. The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus.

4. This work establishes the existence of a bona fide PAX4-enriched cell subpopulation nested within pancreatic islets that can expand in periods of increased functional demands, and exhibit improved viability in response to pathophysiological situations.

5. Pax4 expression is not sufficient to transduce pancreatic alpha cells into beta cells. Overexpression of Pax4 in alpha cells may not increase functional beta cell number in diabetic patients

6. Adult glucagon (show GCG Proteins) producing cells can be converted into beta-like cells upon Pax4 misexpression.

7. RBM4 (show RBM4 Proteins) promoted insulin (show INS Proteins) gene expression by altering the isoform balance of the transcription factors Isl1 (show ISL1 Proteins) and Pax4 via alternative splicing control.

8. these finding demonstrate that, downstream of Neurog3 (show NEUROG3 Proteins), the specification of a subset of enteroendocrine subtypes relies on both Arx and Pax4, while others depend only on Arx or Pax4.

9. Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-kappaB target genes while increasing Bcl-2 (show BCL2 Proteins) levels.

10. Pax4 has a role in facilitating embryonic stem cell differentiation into the pancreatic lineage