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Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor

Glucocorticoid (GC) receptors (GRs) have profound anti-survival effects on human small cell lung cancer (SCLC). To explore the basis of these effects, protein partners for GRs were sought using a yeast two-hybrid screen. We discovered a novel gene, FAM33A, subsequently identified as a SKA1 partner a...

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Autores principales: Rice, Lisa, Waters, Charlotte E, Eccles, Jennifer, Garside, Helen, Sommer, Paula, Kay, Paul, Blackhall, Fiona H, Zeef, Leo, Telfer, Brian, Stratford, Ian, Clarke, Rob, Singh, Dave, Stevens, Adam, White, Anne, Ray, David W
Formato: Texto
Lenguaje:English
Publicado: BioScientifica 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518725/
https://www.ncbi.nlm.nih.gov/pubmed/18583474
http://dx.doi.org/10.1677/JOE-08-0019
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author Rice, Lisa
Waters, Charlotte E
Eccles, Jennifer
Garside, Helen
Sommer, Paula
Kay, Paul
Blackhall, Fiona H
Zeef, Leo
Telfer, Brian
Stratford, Ian
Clarke, Rob
Singh, Dave
Stevens, Adam
White, Anne
Ray, David W
author_facet Rice, Lisa
Waters, Charlotte E
Eccles, Jennifer
Garside, Helen
Sommer, Paula
Kay, Paul
Blackhall, Fiona H
Zeef, Leo
Telfer, Brian
Stratford, Ian
Clarke, Rob
Singh, Dave
Stevens, Adam
White, Anne
Ray, David W
author_sort Rice, Lisa
collection PubMed
description Glucocorticoid (GC) receptors (GRs) have profound anti-survival effects on human small cell lung cancer (SCLC). To explore the basis of these effects, protein partners for GRs were sought using a yeast two-hybrid screen. We discovered a novel gene, FAM33A, subsequently identified as a SKA1 partner and involved in mitosis, and so renamed Ska2. We produced an anti-peptide antibody that specifically recognized full-length human SKA2 to measure expression in human cell lines and tissues. There was a wide variation in expression across multiple cell lines, but none was detected in the liver cell line HepG2. A xenograft model of human SCLC had intense staining and archival tissue revealed SKA2 in several human lung and breast tumours. SKA2 was found in the cytoplasm, where it co-localized with GR, but nuclear expression of SKA2 was seen in breast tumours. SKA2 overexpression increased GC transactivation in HepG2 cells while SKA2 knockdown in A549 human lung epithelial cells decreased transactivation and prevented dexamethasone inhibition of proliferation. GC treatment decreased SKA2 protein levels in A549 cells, as did Staurosporine, phorbol ester and trichostatin A; all agents that inhibit cell proliferation. Overexpression of SKA2 potentiated the proliferative response to IGF-I exposure, and knockdown with shRNA caused cells to arrest in mitosis. SKA2 has recently been identified in HeLa S3 cells as part of a complex, which is critical for spindle checkpoint silencing and exit from mitosis. Our new data show involvement in cell proliferation and GC signalling, with implications for understanding how GCs impact on cell fate.
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spelling pubmed-25187252009-01-27 Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor Rice, Lisa Waters, Charlotte E Eccles, Jennifer Garside, Helen Sommer, Paula Kay, Paul Blackhall, Fiona H Zeef, Leo Telfer, Brian Stratford, Ian Clarke, Rob Singh, Dave Stevens, Adam White, Anne Ray, David W J Endocrinol Regular papers Glucocorticoid (GC) receptors (GRs) have profound anti-survival effects on human small cell lung cancer (SCLC). To explore the basis of these effects, protein partners for GRs were sought using a yeast two-hybrid screen. We discovered a novel gene, FAM33A, subsequently identified as a SKA1 partner and involved in mitosis, and so renamed Ska2. We produced an anti-peptide antibody that specifically recognized full-length human SKA2 to measure expression in human cell lines and tissues. There was a wide variation in expression across multiple cell lines, but none was detected in the liver cell line HepG2. A xenograft model of human SCLC had intense staining and archival tissue revealed SKA2 in several human lung and breast tumours. SKA2 was found in the cytoplasm, where it co-localized with GR, but nuclear expression of SKA2 was seen in breast tumours. SKA2 overexpression increased GC transactivation in HepG2 cells while SKA2 knockdown in A549 human lung epithelial cells decreased transactivation and prevented dexamethasone inhibition of proliferation. GC treatment decreased SKA2 protein levels in A549 cells, as did Staurosporine, phorbol ester and trichostatin A; all agents that inhibit cell proliferation. Overexpression of SKA2 potentiated the proliferative response to IGF-I exposure, and knockdown with shRNA caused cells to arrest in mitosis. SKA2 has recently been identified in HeLa S3 cells as part of a complex, which is critical for spindle checkpoint silencing and exit from mitosis. Our new data show involvement in cell proliferation and GC signalling, with implications for understanding how GCs impact on cell fate. BioScientifica 2008-09 /pmc/articles/PMC2518725/ /pubmed/18583474 http://dx.doi.org/10.1677/JOE-08-0019 Text en © 2008 Society for Endocrinology http://www.endocrinology.org/journals/reuselicence/ This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence (http://www.endocrinology.org/journals/reuselicence/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular papers
Rice, Lisa
Waters, Charlotte E
Eccles, Jennifer
Garside, Helen
Sommer, Paula
Kay, Paul
Blackhall, Fiona H
Zeef, Leo
Telfer, Brian
Stratford, Ian
Clarke, Rob
Singh, Dave
Stevens, Adam
White, Anne
Ray, David W
Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title_full Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title_fullStr Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title_full_unstemmed Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title_short Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor
title_sort identification and functional analysis of ska2 interaction with the glucocorticoid receptor
topic Regular papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518725/
https://www.ncbi.nlm.nih.gov/pubmed/18583474
http://dx.doi.org/10.1677/JOE-08-0019
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