Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene

Rey, Eva Otero; Martín, Juan Enrique Pérez; Barros, Francisco; García‐García, Abel

doi:10.1016/j.oraloncology.2007.02.011

Cited by 45 publications

(39 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to Otero-Rey et al (2008), the V-ATPase C1 subunit appears to be responsible for the assembly of the V0 membrane component and the cytosolic catalytic component (Figure 6). The RAVE complex (a regulator of V-ATPases and endosomal membranes) needs to be present for optimal C subunit and V-ATPase assembly to occur (Forgac, 2007;Smardon and Kane, 2007).…”

Section: The C Subunitmentioning

confidence: 99%

An update in the structure, function, and regulation of V-ATPases: the role of the C subunit

et al. 2012

View full text Add to dashboard Cite

Vacuolar ATPases (V-ATPases) are present in specialized proton secretory cells in which they pump protons across the membranes of various intracellular organelles and across the plasma membrane. The proton transport mechanism is electrogenic and establishes an acidic pH and a positive transmembrane potential in these intracellular and extracellular compartments. V-ATPases have been found to be practically identical in terms of the composition of their subunits in all eukaryotic cells. They have two distinct structures: a peripheral catalytic sector (V1) and a hydrophobic membrane sector (V0) responsible for driving protons. V-ATPase activity is regulated by three different mechanisms, which control pump density, association/dissociation of the V1 and V0 domains, and secretory activity. The C subunit is a 40-kDa protein located in the V1 domain of V-ATPase. The protein is encoded by the ATP6V1C gene and is located at position 22 of the long arm of chromosome 8 (8q22.3). The C subunit has very important functions in terms of controlling the regulation of the reversible dissociation of V-ATPases.Keywords:V-ATPases, proton transport, ATP6V1C1,V1 domain, V0 domain, C subunit. Uma atualização na estrutura, função e regulação das V-ATPases:o papel das subunidades C ResumoAs Vacuolar ATPases (V-ATPases) estão presentes nas células especializadas em secreção de protões, nas quais eles são bombeados através das membranas de vários organelos intracelulares e da membrana plasmática. O mecanismo de transporte de protões é eletrogênico e estabelece um pH ácido e um potencial transmembrana positivo nestes compartimentos intracelulares e extracelulares. As V-ATPases foram encontradas em todas as células eucarióticas, praticamente idênticas em termos de composição das suas subunidades. Elas têm duas estruturas distintas: um setor periférico catalítico (V1) e uma membrana hidrofóbica (V0), responsável pela condução de protões. A atividade das V-ATPases é regulada por três mecanismos diferentes, os quais controlam a densidade de bomba, associação/dissociação de domínios V1 e V0, e a atividade secretora. A subunidade C é uma proteína de 40-kDa, localizada no domínio V1 da V-ATPase. Essa proteína é codificada pelo gene ATP6V1C e está localizada na posição 22 do braço longo do cromossomo 8 (8q22.3). A subunidade C tem funções muito importantes em termos de controle do regulamento da dissociação reversível da V-ATPase.Palavras-chave: V-ATPases, transporte de protões, ATP6V1C1, domínio V1, domínio V0, subunidade C.

show abstract

Section: The C Subunitmentioning

confidence: 99%

An update in the structure, function, and regulation of V-ATPases: the role of the C subunit

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Specific inhibitors of V-ATPase are important because the enzyme is a potential therapeutic target in certain diseases, e.g., osteoporosis, deafness and cancer (Linnett and Beechey 1979;Farina and Gagliardi 1999;Bowman and Bowman 2005;Lu et al 2005;Morimura et al 2008;Otero-Rey et al 2008;Supino et al 2008;Hinton et al 2009;Perez-Sayans et al 2009;McHenry et al 2010;Nishisho et al 2011). The macrolide antibiotics concanamycin A and bafilomycin are the most potent and most selective inhibitors of V-ATPase, with IC 50 values down to the nM region (Bowman et al 1988;Farina and Gagliardi 1999;Gagliardi et al 1999;Huss et al 2002;Dixon et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Estimating the rotation rate in the vacuolar proton-ATPase in native yeast vacuolar membranes

et al. 2012

View full text Add to dashboard Cite

The rate of rotation of the rotor of the yeast vacuolar proton-ATPase (V-ATPase), relative to the stator or the steady parts of enzyme, is estimated in native vacuolar membrane vesicles of Saccharomyces cerevisiae under standardised conditions. Membrane vesicles are spontaneously formed after exposing purified yeast vacuoles to osmotic shock. The fraction of the total ATPase activity originating from V-ATPase is determined using the potent and specific inhibitor of the enzyme, concanamycin A. Inorganic phosphate liberated from ATP in the vacuolar membrane vesicle system, during 10 min of ATPase activity at 20 °C, is assayed spectrophotometrically for different concanamycin A concentrations. A fit to the quadratic binding equation, assuming a single concanamycin A binding site on a monomeric V-ATPase (our data is incompatible with models assuming more binding sites) to the inhibitor titration curve determines the concentration of the enzyme. Combining it with the known rotation:ATP stoichiometry of V-ATPase and the assayed concentration of inorganic phosphate liberated by V-ATPase leads to an average rate of ~9.53 Hz of the 360 degrees rotation, which, according to the time-dependence of the activity, extrapolates to ~14.14 Hz for the beginning of the reaction. These are low limit estimates. To our knowledge this is the first report of the rotation rate in a V-ATPase that is not subjected to genetic or chemical modification and it is not fixed on a solid support, instead it is functioning in its native membrane environment.Special Issue: Structure, function, folding and assembly of membrane proteins -Insight from Biophysics.

show abstract

“…Our research group found a very interesting association between OSCC and overexpression of ATP6V1C1 54, which seems to be the main gene involved in the regulation of V-ATPase enzymes and the acidity of solid oral tumors (54).…”

Section: 88 --------------------------------------------------------mentioning

confidence: 71%

Genetic and molecular alterations associated with oral squamous cell cancer (Review)

Pérez-Sayáns¹

2009

Oncol Rep

101

View full text Add to dashboard Cite

Abstract. The development of oral squamous cell cancer (OSCC) is a multistep process involving the accumulation of multiple genetic alterations modulated by genetic predisposition and environmental influences such as tobacco and alcohol use, chronic inflammation, and viral infections. All of these factors can lead to a wide range of genetic and molecular alterations that can be detected using a range of molecular studies. The alterations mostly affect two large groups of genes: oncogenes and tumor suppressor genes, which can be either inactivated or overexpressed through mutations, loss of heterozygosity, deletions, or epigenetic modifications such as methylation. Other molecules that are closely associated with tumor pathogenesis and prognosis also exist and warrant further study. Important advances in molecular biology are helping to shed light on oral cancer and thus aiding in the early diagnosis and development of new personalized treatment approaches. The purpose of the review is to explore the genetic and molecular alterations associated with OSCC.

show abstract

Intracellular pH regulation in oral squamous cell carcinoma is mediated by increased V-ATPase activity via over-expression of the ATP6V1C1 gene

Cited by 45 publications

References 32 publications

An update in the structure, function, and regulation of V-ATPases: the role of the C subunit

An update in the structure, function, and regulation of V-ATPases: the role of the C subunit

Estimating the rotation rate in the vacuolar proton-ATPase in native yeast vacuolar membranes

Genetic and molecular alterations associated with oral squamous cell cancer (Review)

Contact Info

Product

Resources

About