A single mutation in Securin induces chromosomal instability and enhances cell invasion
Pituitary tumour transforming gene (pttg1) encodes Securin, a protein involved in the inhibition of sister chromatid separation binding to Separase until the onset of anaphase. Separase is a cysteine-protease that degrades cohesin to segregate the sister chromatids to opposite poles of the cell. The...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/165833 |
| Acceso en línea: | https://hdl.handle.net/11441/165833 https://doi.org/10.1016/j.ejca.2012.06.024 |
| Access Level: | acceso abierto |
| Palabra clave: | Securin pttg Cell invasiveness Tumourigenesis Chromosomal instability Pituitary tumour Human mutation |
| id |
ES_e2d269c5d292fca2729bf2ca53a9866b |
|---|---|
| oai_identifier_str |
oai:idus.us.es:11441/165833 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
A single mutation in Securin induces chromosomal instability and enhances cell invasionMora Santos, María del MarCastilla, CarolinaHerrero Ruiz, JoaquínGiráldez Macías, ServandoLimón Mortés, María CristinaSáez, CarmenJapón Rodríguez, Miguel ÁngelTortolero García, María DoloresRomero Portillo, FranciscoSecurinpttgCell invasivenessTumourigenesisChromosomal instabilityPituitary tumourHuman mutationPituitary tumour transforming gene (pttg1) encodes Securin, a protein involved in the inhibition of sister chromatid separation binding to Separase until the onset of anaphase. Separase is a cysteine-protease that degrades cohesin to segregate the sister chromatids to opposite poles of the cell. The amount of Securin is strongly regulated because it should allow Separase activation when it is degraded by the anaphase promoting complex/cyclosome, should arrest the cell cycle after DNA damage, when it is degraded through SKP1-CUL1-βTrCP ubiquitin ligase, and its overexpression induces tumour formation and correlates with metastasis in multiple tumours. Securin is a phosphoprotein that contains 32 potentially phosphorylatable residues. We mutated and analysed most of them, and found a single mutant, hSecT60A, that showed enhanced oncogenic properties. Our fluorescence activated cell sorting analysis, fluorescence in situ hybridisation assays, tumour cell migration and invasion experiments and gene expression by microarrays analysis clearly involved hSecT60A in chromosomal instability and cell invasion. These results show, for the first time, that a single mutation in pttg1 is sufficient to trigger the oncogenic properties of Securin. The finding of this point mutation in patients might be used as an effective strategy for early detection of cancer.Ministerio de Ciencia e Innovación (SAF2011-30003)Ministerio de Sanidad (Red de Biobancos RD09/0076/ 00085)Dirección General de Investigación, Tecnología y Empresa, J.A. (P08-CVI-03603 and P10-CTS-06243) and Consejería de Salud, J.A. (PI-2009-0589 and AI2011-001)ElsevierMicrobiologíaMinisterio de Ciencia e InnovaciónMinisterio de Sanidad. EspañaJunta de Andalucía2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/165833https://doi.org/10.1016/j.ejca.2012.06.024reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésEuropean Journal of Cancer, 49 (2), 500-510.SAF2011-30003RD09/0076/ 00085P08-CVI-03603P10-CTS-06243PI-2009-0589AI2011-001https://dx.doi.org/10.1016/j.ejca.2012.06.024info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1658332026-06-17T12:51:07Z |
| dc.title.none.fl_str_mv |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| title |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| spellingShingle |
A single mutation in Securin induces chromosomal instability and enhances cell invasion Mora Santos, María del Mar Securin pttg Cell invasiveness Tumourigenesis Chromosomal instability Pituitary tumour Human mutation |
| title_short |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| title_full |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| title_fullStr |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| title_full_unstemmed |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| title_sort |
A single mutation in Securin induces chromosomal instability and enhances cell invasion |
| dc.creator.none.fl_str_mv |
Mora Santos, María del Mar Castilla, Carolina Herrero Ruiz, Joaquín Giráldez Macías, Servando Limón Mortés, María Cristina Sáez, Carmen Japón Rodríguez, Miguel Ángel Tortolero García, María Dolores Romero Portillo, Francisco |
| author |
Mora Santos, María del Mar |
| author_facet |
Mora Santos, María del Mar Castilla, Carolina Herrero Ruiz, Joaquín Giráldez Macías, Servando Limón Mortés, María Cristina Sáez, Carmen Japón Rodríguez, Miguel Ángel Tortolero García, María Dolores Romero Portillo, Francisco |
| author_role |
author |
| author2 |
Castilla, Carolina Herrero Ruiz, Joaquín Giráldez Macías, Servando Limón Mortés, María Cristina Sáez, Carmen Japón Rodríguez, Miguel Ángel Tortolero García, María Dolores Romero Portillo, Francisco |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Microbiología Ministerio de Ciencia e Innovación Ministerio de Sanidad. España Junta de Andalucía |
| dc.subject.none.fl_str_mv |
Securin pttg Cell invasiveness Tumourigenesis Chromosomal instability Pituitary tumour Human mutation |
| topic |
Securin pttg Cell invasiveness Tumourigenesis Chromosomal instability Pituitary tumour Human mutation |
| description |
Pituitary tumour transforming gene (pttg1) encodes Securin, a protein involved in the inhibition of sister chromatid separation binding to Separase until the onset of anaphase. Separase is a cysteine-protease that degrades cohesin to segregate the sister chromatids to opposite poles of the cell. The amount of Securin is strongly regulated because it should allow Separase activation when it is degraded by the anaphase promoting complex/cyclosome, should arrest the cell cycle after DNA damage, when it is degraded through SKP1-CUL1-βTrCP ubiquitin ligase, and its overexpression induces tumour formation and correlates with metastasis in multiple tumours. Securin is a phosphoprotein that contains 32 potentially phosphorylatable residues. We mutated and analysed most of them, and found a single mutant, hSecT60A, that showed enhanced oncogenic properties. Our fluorescence activated cell sorting analysis, fluorescence in situ hybridisation assays, tumour cell migration and invasion experiments and gene expression by microarrays analysis clearly involved hSecT60A in chromosomal instability and cell invasion. These results show, for the first time, that a single mutation in pttg1 is sufficient to trigger the oncogenic properties of Securin. The finding of this point mutation in patients might be used as an effective strategy for early detection of cancer. |
| publishDate |
2013 |
| dc.date.none.fl_str_mv |
2013 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11441/165833 https://doi.org/10.1016/j.ejca.2012.06.024 |
| url |
https://hdl.handle.net/11441/165833 https://doi.org/10.1016/j.ejca.2012.06.024 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
European Journal of Cancer, 49 (2), 500-510. SAF2011-30003 RD09/0076/ 00085 P08-CVI-03603 P10-CTS-06243 PI-2009-0589 AI2011-001 https://dx.doi.org/10.1016/j.ejca.2012.06.024 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
reponame:idUS. Depósito de Investigación de la Universidad de Sevilla instname:Universidad de Sevilla (US) |
| instname_str |
Universidad de Sevilla (US) |
| reponame_str |
idUS. Depósito de Investigación de la Universidad de Sevilla |
| collection |
idUS. Depósito de Investigación de la Universidad de Sevilla |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869422445373423616 |
| score |
15,812429 |