Liprin-α4 is a new hypoxia-inducible target gene required for maintenance of cell-cell contacts.
Liprin-α1 to liprin-α4 constitute a family of cytoplasmic proteins, which have been found in various multiprotein complexes. For liprin-α1 roles in synapse formation and cell spreading were described but other liprin family members are not well characterized. We show here that liprin-α4 is upregulated in human clear cell renal cell carcinomas (RCC) as compared to normal kidney tissue. Liprin-α4 expression is downregulated by the von Hippel-Lindau tumor suppressor (VHL) and upregulated by hypoxia in RCC cell lines. The liprin-α4 gene promoter is directly activated by binding of the hypoxia-inducible factor 1α (HIF-1α) to HRE consensus binding sites as shown by reporter assays and chromatin immunoprecipitations. RNAi mediated knockdown of liprin-α4 leads to reduced E-cadherin and β-catenin levels at cell junctions and to dissociation of epithelial cell contacts. Our data describe for the first time liprin-α4 as a hypoxia-induced gene potentially involved in cell-cell adhesion.
Mattauch
Sandra
S
Nikolaus Fiebiger Center, University Erlangen-Nürnberg, Glückstrasse 6, Erlangen, Germany.
Sachs
Martin
M
Behrens
Jürgen
J
D015820:Cadherins / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000032:analysis
D015820:Cadherins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051176:beta Catenin; C553328:PPFIA4 protein, human; D054557:Receptor-Like Protein Tyrosine Phosphatases