Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization.
CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC. Although its expression pattern in psoriatic skin differs from healthy skin and its overexpression influences cel...
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2012
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oai:doaj.org-article:e766049596e5457c8f30b1ee4cca5b822021-11-18T08:07:36ZCentrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization.1932-620310.1371/journal.pone.0049920https://doaj.org/article/e766049596e5457c8f30b1ee4cca5b822012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189171/?tool=EBIhttps://doaj.org/toc/1932-6203CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC. Although its expression pattern in psoriatic skin differs from healthy skin and its overexpression influences cell proliferation in transgenic mice, its role as a psoriasis effector gene has remained unsettled. The 5'-region of the gene contains a SNP (rs3130453) that controls a 5'-extended open reading frame and thus the translation of alternative isoforms. We have now compared the function of two CCHCR1 isoforms: the novel longer isoform 1 and the previously studied isoform 3. In samples of Finnish and Swedish families, the allele generating only isoform 3 shows association with psoriasis (P<10(-7)). Both isoforms localize at the centrosome, a cell organelle playing a role in cell division. In stably transfected cells the isoform 3 affects cell proliferation and with the CCHCR1*WWCC allele, also apoptosis. Furthermore, cells overexpressing CCHCR1 show isoform- and haplotype-specific influences in the cell size and shape and alterations in the organization and expression of the cytoskeletal proteins actin, vimentin, and cytokeratins. The isoform 1 with the non-risk allele induces the expression of keratin 17, a hallmark for psoriasis; the silencing of CCHCR1 reduces its expression in HEK293 cells. CCHCR1 also regulates EGF-induced STAT3 activation in an isoform-specific manner: the tyrosine phosphorylation of STAT3 is disturbed in isoform 3-transfected cells. The centrosomal localization of CCHCR1 provides a connection to the abnormal cell proliferation and offers a link to possible cellular pathways altered in psoriasis.Mari H TervaniemiH Annika SiitonenCilla SöderhällGurinder MinhasJyrki VuolaInkeri TialaRaija SormunenLena SamuelssonSari SuomelaJuha KereOuti ElomaaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49920 (2012) |
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Medicine R Science Q Mari H Tervaniemi H Annika Siitonen Cilla Söderhäll Gurinder Minhas Jyrki Vuola Inkeri Tiala Raija Sormunen Lena Samuelsson Sari Suomela Juha Kere Outi Elomaa Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| description |
CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC. Although its expression pattern in psoriatic skin differs from healthy skin and its overexpression influences cell proliferation in transgenic mice, its role as a psoriasis effector gene has remained unsettled. The 5'-region of the gene contains a SNP (rs3130453) that controls a 5'-extended open reading frame and thus the translation of alternative isoforms. We have now compared the function of two CCHCR1 isoforms: the novel longer isoform 1 and the previously studied isoform 3. In samples of Finnish and Swedish families, the allele generating only isoform 3 shows association with psoriasis (P<10(-7)). Both isoforms localize at the centrosome, a cell organelle playing a role in cell division. In stably transfected cells the isoform 3 affects cell proliferation and with the CCHCR1*WWCC allele, also apoptosis. Furthermore, cells overexpressing CCHCR1 show isoform- and haplotype-specific influences in the cell size and shape and alterations in the organization and expression of the cytoskeletal proteins actin, vimentin, and cytokeratins. The isoform 1 with the non-risk allele induces the expression of keratin 17, a hallmark for psoriasis; the silencing of CCHCR1 reduces its expression in HEK293 cells. CCHCR1 also regulates EGF-induced STAT3 activation in an isoform-specific manner: the tyrosine phosphorylation of STAT3 is disturbed in isoform 3-transfected cells. The centrosomal localization of CCHCR1 provides a connection to the abnormal cell proliferation and offers a link to possible cellular pathways altered in psoriasis. |
| format |
article |
| author |
Mari H Tervaniemi H Annika Siitonen Cilla Söderhäll Gurinder Minhas Jyrki Vuola Inkeri Tiala Raija Sormunen Lena Samuelsson Sari Suomela Juha Kere Outi Elomaa |
| author_facet |
Mari H Tervaniemi H Annika Siitonen Cilla Söderhäll Gurinder Minhas Jyrki Vuola Inkeri Tiala Raija Sormunen Lena Samuelsson Sari Suomela Juha Kere Outi Elomaa |
| author_sort |
Mari H Tervaniemi |
| title |
Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| title_short |
Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| title_full |
Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| title_fullStr |
Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| title_full_unstemmed |
Centrosomal localization of the psoriasis candidate gene product, CCHCR1, supports a role in cytoskeletal organization. |
| title_sort |
centrosomal localization of the psoriasis candidate gene product, cchcr1, supports a role in cytoskeletal organization. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/e766049596e5457c8f30b1ee4cca5b82 |
| work_keys_str_mv |
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