Characterization of the activation of protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1) by hypoxia inducible factor-2 alpha.

摘要: Background: Hypoxia inducible factors (HIFs) are the principal means by which cells upregulate genes in response to hypoxia and certain other stresses. There two major HIFs, HIF-1 HIF-2. We previously found that preferentially activated One was protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1). PTPRZ1 is overexpressed a number of tumors has been implicated glioblastoma pathogenesis. Methodology/Principal Findings: To understand preferential activation HIF-2, we studied promoter HEK293T Hep3B cells. Through deletion mutational analysis, identified element. This element bound both further role for ELK1, an E26 transformationspecific (Ets) factor can bind HIF-2a but not HIF-1a, HIF-2 responsiveness. Knock-down experiments using siRNA ELK1 decreased over 50%. Also, mutation one Ets binding motifs located near similarly Finally, chromatin immunoprecipitation assays showed HIF region. Conclusions/Significance: These results identify HIF-binding Ets-binding on provide evidence at least part from cooperative nearby sites may have implications tumor pathogenesis understanding neurobiology, help inform development novel therapy.