Liprin-[alpha]4 is a new hypoxia-inducible target gene required for maintenance of cell-cell contacts
Liprin-[alpha]1 to liprin-[alpha]4 constitute a family of cytoplasmic proteins, which have been found in various multiprotein complexes. For liprin-[alpha]1 roles in synapse formation and cell spreading were described but other liprin family members are not well characterized. We show here that lipr...
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Veröffentlicht in: | Experimental cell research 2010-10, Vol.316 (17), p.2883 |
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Sprache: | eng |
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Zusammenfassung: | Liprin-[alpha]1 to liprin-[alpha]4 constitute a family of cytoplasmic proteins, which have been found in various multiprotein complexes. For liprin-[alpha]1 roles in synapse formation and cell spreading were described but other liprin family members are not well characterized. We show here that liprin-[alpha]4 is upregulated in human clear cell renal cell carcinomas (RCC) as compared to normal kidney tissue. Liprin-[alpha]4 expression is downregulated by the von Hippel-Lindau tumor suppressor (VHL) and upregulated by hypoxia in RCC cell lines. The liprin-[alpha]4 gene promoter is directly activated by binding of the hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) to HRE consensus binding sites as shown by reporter assays and chromatin immunoprecipitations. RNAi mediated knockdown of liprin-[alpha]4 leads to reduced E-cadherin and [beta]-catenin levels at cell junctions and to dissociation of epithelial cell contacts. Our data describe for the first time liprin-[alpha]4 as a hypoxia-induced gene potentially involved in cell-cell adhesion. [PUBLICATION ABSTRACT] |
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ISSN: | 0014-4827 1090-2422 |
DOI: | 10.1016/j.yexcr.2010.06.022 |