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. Structured summary: MINT-7293982: E-cadherin (uniprotkb:Q95LE0) and CA IX (genbank_protein_gi:223556027) colocalize (MI:0403) by fluorescence microscopy (MI:0416) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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Gazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, TurkeyGazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, Turkey
Uslu, Azize Gizem
Maz, Tugce Gur
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Gazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, TurkeyGazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, Turkey
Maz, Tugce Gur
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Nocentini, Alessio
Banoglu, Erden
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Gazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, TurkeyGazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, Turkey
Banoglu, Erden
Supuran, Claudiu T.
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Univ Florence, Sez Sci Farmaceut, NEUROFARBA Dept, Via Ugo Schiff 6, I-50019 Florence, ItalyGazi Univ, Fac Pharm, Dept Pharmaceut Chem, Tac Sok 3, TR-06560 Ankara, Turkey
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G Pulla Reddy Coll Pharm, Dept Biotechnol, Hyderabad 500028, IndiaNatl Inst Pharmaceut Educ & Res, Dept Med Chem, Hyderabad, Balanagar, India
Alvala, Ravi
Alvala, Mallika
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Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Hyderabad, Balanagar, India
MARS Training Acad, Hyderabad 500028, IndiaNatl Inst Pharmaceut Educ & Res, Dept Med Chem, Hyderabad, Balanagar, India