The T-box transcription factor TBX3 drives proliferation by direct repression of the p21WAF1 cyclin-dependent kinase inhibitor

 

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dc.contributor.author Willmer, Tarryn
dc.contributor.author Hare, Shannagh
dc.contributor.author Peres, Jade
dc.contributor.author Prince, Sharon
dc.date.accessioned 2016-05-23T06:55:28Z
dc.date.available 2016-05-23T06:55:28Z
dc.date.issued 2016-04-22
dc.identifier.citation Willmer, T., Hare, S., Peres, J., & Prince, S. (2016). The T-box transcription factor TBX3 drives proliferation by direct repression of the p21 WAF1 cyclin-dependent kinase inhibitor. Cell Division, 11(1), 1. en_ZA
dc.identifier.issn 1747-1028 en_ZA
dc.identifier.uri http://dx.doi.org/10.1186/s13008-016-0019-0
dc.identifier.uri http://hdl.handle.net/11427/19767
dc.description.abstract Background: TBX3, a member of the T-box family of transcription factors, is essential in development and has emerged as an important player in the oncogenic process. TBX3 is overexpressed in several cancers and has been shown to contribute directly to tumour formation, migration and invasion. However, little is known about the molecular basis for its role in development and oncogenesis because there is a paucity of information regarding its target genes. The cyclin-dependent kinase inhibitor p21WAF1 plays a pivotal role in a myriad of processes including cell cycle arrest, senescence and apoptosis and here we provide a detailed mechanism to show that it is a direct and biologically relevant target of TBX3. Results: Using a combination of luciferase reporter gene assays and in vitro and in vivo binding assays we show that TBX3 directly represses the p21WAF1 promoter by binding a T-element close to its initiator. Furthermore, we show that the TBX3 DNA binding domain is required for the transcriptional repression of p21WAF1 and that pseudo-phosphorylation of a serine proline motif (S190) located within this domain may play an important role in regulating this ability. Importantly, we demonstrate using knockdown and overexpression experiments that p21WAF1 repression by TBX3 is biologically significant and required for TBX3-induced cell proliferation of chondrosarcoma cells. Conclusions: Results from this study provide a detailed mechanism of how TBX3 transcriptionally represses p21WAF1 which adds to our understanding of how it may contribute to oncogenesis. en_ZA
dc.language eng en_ZA
dc.publisher BioMed Central en_ZA
dc.rights Creative Commons Attribution 4.0 International (CC BY 4.0) *
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en_ZA
dc.source Cell Division en_ZA
dc.source.uri http://celldiv.biomedcentral.com/
dc.subject Transcription factor
dc.subject p21WAF1
dc.subject Cancer
dc.title The T-box transcription factor TBX3 drives proliferation by direct repression of the p21WAF1 cyclin-dependent kinase inhibitor en_ZA
dc.type Journal Article en_ZA
dc.date.updated 2016-05-19T09:29:04Z
dc.language.rfc3066 en
dc.rights.holder Willmer et al.
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Human Biology en_ZA
uct.type.filetype Text
uct.type.filetype Image


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