For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
53
views
28
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      431
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Overlapping ATP2C1 and ASTE1 Genes in Human Genome: Implications for SPCA1 Expression?

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The ATP2C1 gene encodes for the secretory pathway calcium (Ca 2+)-ATPase pump (SPCA1), which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic organization between mouse and human we speculate that the overlap between ATP2C1 and ASTE1 genes only in humans could explain this different response to ATP2C1 dysregulation. We propose that ASTE1, overlapping with ATP2C1 in humans, affects alternative splicing, and potentially protein expression of the latter. If dysregulated, the composition of the SPCA1 isoform pool could diverge from the physiological status, affecting cytosolic Ca 2+-signaling, and in turn perturbing cell division, leading to cell death or to neoplastic transformation.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Store-independent activation of Orai1 by SPCA2 in mammary tumors.

          Mingye Feng, Desma Grice, Helen M. Faddy … (2010)
          Ca(2+) is an essential and ubiquitous second messenger. Changes in cytosolic Ca(2+) trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca(2+)-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca(2+) levels and tumorigenicity. Contrary to its conventional role in Golgi Ca(2+) sequestration, expression of SPCA2 increased Ca(2+) influx by a mechanism dependent on the store-operated Ca(2+) channel Orai1. Unexpectedly, SPCA2-Orai1 signaling was independent of ER Ca(2+) stores or STIM1 and STIM2 sensors and uncoupled from Ca(2+)-ATPase activity of SPCA2. Binding of the SPCA2 amino terminus to Orai1 enabled access of its carboxyl terminus to Orai1 and activation of Ca(2+) influx. Our findings reveal a signaling pathway in which the Orai1-SPCA2 complex elicits constitutive store-independent Ca(2+) signaling that promotes tumorigenesis. Copyright © 2010 Elsevier Inc. All rights reserved.
          Article 0 comments Cited 89 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations.

            Alexandre Rouquette-Jazdanian, Frederic Fiore, Valérie Laurent … (2009)
            Colorectal cancers with microsatellite instability are characterized by an important density of tumor-infiltrating lymphocytes and a good prognosis. Microsatellite instability results from the inactivation of the DNA mismatch repair system and induces secondary somatic frameshift mutations within target genes harboring repeat sequences in their coding frame. By disrupting the open reading frame, frameshift mutations can result in the appearance of potentially immunogenic neopeptides. To determine the frameshift mutations inducing a T-cell response during the development of a tumor with microsatellite instability, we studied in 61 colorectal cancer patients with microsatellite instability, using a fluorescent multiplex PCR comparative analysis, the relative frequency of frameshift mutations within 19 target genes and analyzed the correlation of these frameshift mutations with the density of CD3+ tumor-infiltrating lymphocytes. The four most frequently mutated genes were ACVR2 (92%), TAF1B (84%), ASTE1/HT001 (80%) and TGFBR2 (77%). The vast majority (95%) of the tumors exhibited at least three frameshift mutations, and the number of frameshift mutations was associated with tumor progression (TNM stage, wall invasion and tumor diameter). Tumor-infiltrating lymphocyte density was associated with the overall number of frameshift mutations and with the presence of frameshift mutations within two target genes, namely ASTE1/HT001 and PTEN. These results strongly argue for the clinical relevance of immunotherapy of colorectal cancers with microsatellite instability.
            Article 0 comments Cited 79 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.

              Z. Hu, T Mauro, G Bench … (2000)
              Hailey-Hailey disease (HHD, MIM 16960) is inherited in an autosomal dominant manner and characterized by persistent blisters and erosions of the skin. Impaired intercellular adhesion and epidermal blistering also occur in individuals with pemphigus (which is due to autoantibodies directed against desmosomal proteins) and in patients with Darier disease (DD, MIM 124200), which is caused by mutations in a gene encoding a sarco/endoplasmic reticulum (ER)-Golgi calcium pump. We report here the identification of mutations in ATP2C1, encoding the human homologue of an ATP-powered pump that sequesters calcium into the Golgi in yeast, in 21 HHD kindreds. Regulation of cytoplasmic calcium is impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient is attenuated in vivo in HHD patients. Our findings not only provide an understanding of the molecular basis of HHD, but also underscore the importance of calcium control to the functioning of stratified squamous epithelia.
              Article 0 comments Cited 73 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date Collection: January 2013
                Publication date (Electronic): 04 January 2013
                Volume: 14
                Issue: 1
                Pages: 674-683
                Affiliations
                [1 ]School of Biosciences, University of Exeter, Exeter, England EX4 4QD, UK
                [2 ]Division of Molecular Cell Biology, Institute for Molecular Bioscience, the University of Queensland, 306 Carmody Road, St. Lucia, Brisbane QLD 4072, Australia
                [3 ]Faculty of Health Sciences, The Southbank Institute of Technology, 66 Ernest Street, South Brisbane QLD 4101, Australia; E-Mail: l.malquori@ 123456gmail.com
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: m.micaroni@ 123456imb.uq.edu.au ; Tel.: +61-7-3346-2035.
                Article
                Publisher ID: ijms-14-00674
                DOI: 10.3390/ijms14010674
                PMC ID: 3565288
                PubMed ID: 23344038
                SO-VID: 3a707806-bc96-4390-9bd6-b77b6df4281f
                Copyright © © 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 20 November 2012
                Date revision received : 05 December 2012
                Date accepted : 07 December 2012
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: aste1,atp2c1,atpase ca2+ pump,gene expression,golgi apparatus,hailey-hailey disease,intracellular membrane trafficking,spca1
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: aste1, atp2c1, atpase ca2+ pump, gene expression, golgi apparatus, hailey-hailey disease, intracellular membrane trafficking, spca1

                Comments

                Comment on this article

                scite_

                Similar content431

                See all similar

                Cited by3

                See all cited by

                Most referenced authors1,028

                See all reference authors