Swarts, Dorian Rein Andreas orcid.org/0000-0002-7927-7613, Stewart, Emma Rachael, Higgins, Gillian Sarah et al. (1 more author) (2018) CIZ1-F, an alternatively spliced variant of the DNA replication protein CIZ1 with distinct expression and localisation, is overrepresented in early stage common solid tumours. Cell cycle. ISSN 1551-4005
Abstract
CIZ1 promotes cyclin-dependent DNA replication and resides in sub-nuclear foci that are part of the protein nuclear matrix (NM), and in RNA assemblies that are enriched at the inactive X chromosome (Xi) in female cells. It is subjected to alternative splicing, with specific variants implicated in adult and paediatric cancers. CIZ1-F is characterized by a frame shift that results from splicing exons 8-12 leading to inclusion of a short alternative reading frame (ARF), excluding the previously characterized C-terminal NM anchor domain. Here, we apply a set of novel variant-selective molecular tools targeted to the ARF to profile the expression of CIZ1-F at both transcript and protein levels, with focus on its relationship with the RNA-dependent and -independent fractions of the NM. Unlike full-length CIZ1, CIZ1-F does not accumulate at Xi, though like full-length CIZ1 it does resist extraction with DNase. Notably, CIZ1-F is sensitive to RNase identifying it as part of the RNA-fraction of the NM. In quiescent cells CIZ1-F transcript expression is suppressed and CIZ1-F protein is excluded from the nucleus, with re-expression not observed until the second cell cycle after exit from quiescence. Importantly, CIZ1-F is over-expressed in common solid tumours including colon and breast, pronounced in early stage but not highly-proliferative late stage tumours. Moreover, expression was significantly higher in hormone receptor negative breast tumours than receptor positive tumours. Together these data show that CIZ1-F is expressed in proliferating cells in an unusual cell cycle-dependent manner, and suggest that it may have potential as a tumour biomarker.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Author(s). Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 01 Oct 2018 11:20 |
Last Modified: | 08 Feb 2025 00:31 |
Published Version: | https://doi.org/10.1080/15384101.2018.1526600 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1080/15384101.2018.1526600 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:136435 |
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Description: CIZ1 F an alternatively spliced variant of the DNA replication protein CIZ1 with distinct expression and localisation is overrepresented in early
Licence: CC-BY 2.5