Expression of the Hypoxia Marker Carbonic Anhydrase IX Is Critically Dependent on SP1 Activity. Identification of a Novel Type of Hypoxia-responsive Enhancer

摘要: In the present study, we further studied mechanisms of transcriptional regulation tumor-associated carbonic anhydrase IX (CAIX). We identifiedPR5 in CA9 promoter as another SP1/SP3-binding site. As shown by electromobility shift assays and block-replacement mutagenesis, PR5 is functionally equivalent to PR1 identified previously. However, there a strong requirement for SP1/SP3 activity position, from position cannot compensate this. various cell lines, expression endogenous CAIX constructs depend on demonstrated dose-dependent inhibitory effect SP1 inhibitor mithramycin A. The two conditions induction described previously differ their sensitivity A inhibition; hypoxia-mimic-induced less sensitive than density (mild hypoxia)-induced expression. Our study highlights importance provides additional evidence distinct responsible true mild hypoxia-induced presence element absolutely required activity, it significantly up-regulates hypoxic induction. hypoxia-response thus may represent novel type enhancer capable mounting responses wider range conditions.