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Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells (Articolo in rivista)

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Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells (Articolo in rivista) (literal)

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Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M, Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N (2013)
Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells
in Journal of proteome research (Print); ACS, American chemical society, Washington, DC (Stati Uniti d'America)
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Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M, Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N (literal)

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CEINGE Biotecnologie Avanzate SCaRL, Naples, Italy Proteomics and Mass Spectrometry Laboratory, ISPAAM, CNR, Naples, Italy Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita? di Napoli Federico II, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita? di Napoli Federico II, Italy Department of Public Health, Section of Pathology, Seconda Universita? di Napoli, Italy Dipartimento di Scienze Biomorfologiche e Funzionali, Universita? di Napoli Federico II, Italy Department of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic Laboratorio di Chimica Bioinorganica, Universita? di Firenze, Italy (literal)

Titolo

Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells (literal)

Abstract

Carbonic anhydrase IX (CA IX) is a trans. membrane protein affecting pH regulation, cell migration/invasion, and survival in hypoxic tumors. Although the pathways related to CA IX have begun to emerge, molecular partners mediating its functions remain largely unknown. Here we characterize the CA IX interactome in hypoxic HEK-293 cells. Most of the identified CA IX-binding partners contain the HEAT/ARM repeat domain and belong to the nuclear transport machinery. We show that the interaction with two of these proteins, namely XPO1 exportin and TNPO1 importin, occurs via the C-terminal region of CA IX and increases with protein phosphorylation. We also demonstrate that nuclear CA IX is enriched in hypoxic cells and is present in renal cell carcinoma tissues. These data place CA IX among the cell-surface signal transducers undergoing nuclear translocation. Accordingly, CA IX interactome involves also CAND1, which participates in both gene transcription and assembly of SCF ubiquitin ligase complexes. It is noteworthy that down-regulation of CAND1 leads to decreased CA IX protein levels apparently via affecting its stability. Our findings provide the first evidence that CA IX interacts with proteins involved in nuclear/cytoplasmic transport, gene transcription, and protein stability, and suggest the existence of nuclear CA IX protein subpopulations with a potential intracellular function, distinct from the crucial CA IX role at the cell surface. (literal)

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