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

被引：29

作者：

Hulikova, Alzbeta ^{[1
]}

Zatovicova, Miriam ^{[1
]}

Svastova, Eliska ^{[1
]}

Ditte, Peter ^{[1
]}

Brasseur, Robert ^{[2
]}

Kettmann, Richard ^{[3
]}

Supuran, Claudiu T. ^{[4
]}

Kopacek, Juraj ^{[1
]}

Pastorek, Jaromir ^{[1
]}

Pastorekova, Silvia ^{[1
]}

机构：

[1] Slovak Acad Sci, Inst Virol, Bratislava 84505, Slovakia

[2] Fac Sci Agronom Gembloux, Ctr Biophys Mol Numer, B-5030 Gembloux, Belgium

[3] Fac Sci Agronom Gembloux, B-5030 Gembloux, Belgium

[4] Univ Florence, Lab Chim Bioinorgan, I-50019 Florence, Italy

来源：

FEBS LETTERS | 2009年 / 583卷 / 22期

关键词：

Carbonic anhydrase IX; pH regulation; Cell adhesion; Ectodomain shedding; Hypoxia; Acidosis; PROTEIN-PROTEIN INTERACTIONS; DOMAIN; PH; TRANSMEMBRANE; CANCER; INHIBITORS; RESIDUES; ADHESION; BINDING; GROWTHS;

D O I：

10.1016/j.febslet.2009.10.060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3563 / 3568

页数：6

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