Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-induced enzyme involved in pH regulation and cell adhesion. Its catalytically active ectodomain (ECD) is linked to a transmembrane region and a short intracellular (IC) tail. Removal of the IC tail causes intracellular localization of CA IX. Mutations of basic amino acids within IC do not perturb the membrane position, but reduce shedding of the CA IX ectodomain as well as CA IX-mediated cell dissociation. Moreover, they abolish the CA IX capacity to acidify extracellular pH (pHe) and bind CA IX-selective sulfonamide inhibitor in hypoxia. These findings provide the first evidence for the critical contribution of the IC tail to the proper functioning of CA IX.

Intact intracellular tail is critical for proper functioning of the tumor-associated, hypoxia-regulated carbonic anhydrase IX / A. Hulikova;M. Zatovicova;E. Svastova;P. Ditte;R. Brasseur;R. Kettmann;C. T. Supuran;J. Kopacek;J. Pastorek;S. Pastorekova. - In: FEBS LETTERS. - ISSN 0014-5793. - STAMPA. - 583:(2009), pp. 3563-3568. [10.1016/j.febslet.2009.10.060]

Intact intracellular tail is critical for proper functioning of the tumor-associated, hypoxia-regulated carbonic anhydrase IX.

SUPURAN, CLAUDIU TRANDAFIR;
2009

Abstract

Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-induced enzyme involved in pH regulation and cell adhesion. Its catalytically active ectodomain (ECD) is linked to a transmembrane region and a short intracellular (IC) tail. Removal of the IC tail causes intracellular localization of CA IX. Mutations of basic amino acids within IC do not perturb the membrane position, but reduce shedding of the CA IX ectodomain as well as CA IX-mediated cell dissociation. Moreover, they abolish the CA IX capacity to acidify extracellular pH (pHe) and bind CA IX-selective sulfonamide inhibitor in hypoxia. These findings provide the first evidence for the critical contribution of the IC tail to the proper functioning of CA IX.
2009
583
3563
3568
A. Hulikova;M. Zatovicova;E. Svastova;P. Ditte;R. Brasseur;R. Kettmann;C. T. Supuran;J. Kopacek;J. Pastorek;S. Pastorekova
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/776181
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