Regulation of expression by promoters versus internal ribosome entry site in the 5′-untranslated sequence of the human cyclin-dependent kinase inhibitor p27

dc.contributor.authorLiu, Zhaoqian
dc.contributor.authorDong, Zizheng
dc.contributor.authorHan, Baoguang
dc.contributor.authorYang, Youyun
dc.contributor.authorLiu, Yang
dc.contributor.authorZhang, Jian-Ting
dc.contributor.departmentPharmacology and Toxicology, School of Medicineen_US
dc.date.accessioned2020-12-11T18:10:47Z
dc.date.available2020-12-11T18:10:47Z
dc.date.issued2005-07-01
dc.description.abstractp27 kip1 regulates cell proliferation by binding to and inhibiting the activity of cyclin-dependent kinases and its expression oscillates with cell cycle. Recently, it has been suggested from studies using the traditional dicistronic DNA assay that the expression of p27 kip1 is regulated by internal ribosome entry site (IRES)-mediated translation initiation, and several RNA-binding protein factors were thought to play some role in this regulation. Considering the inevitable drawbacks of the dicistronic DNA assay, which could mislead a promoter activity or alternative splicing to IRES as previously demonstrated, we decided to reanalyze the 5′-untranslated region (5′-UTR) sequence of p27 kip1 and test whether it contains an IRES element or a promoter using more stringent methods, such as dicistronic RNA and promoterless dicistronic and monocistronic DNA assays. We found that the 5′-UTR sequence of human p27 kip1 does not have any significant IRES activity. The previously observed IRES activities are likely generated from the promoter activities present in the 5′-UTR sequences of p27 kip1 . The findings in this study indicate that transcriptional regulation likely plays an important role in p27 kip1 expression, and the mechanism of regulation of p27 expression by RNA-binding factors needs to be re-examined. The findings in this study also further enforce the importance that more stringent studies, such as promoterless dicistronic and monocistronic DNA and dicistronic RNA tests, are required to safeguard any future claims of cellular IRES.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationZhaoqian Liu, Zizheng Dong, Baoguang Han, Youyun Yang, Yang Liu, Jian-Ting Zhang, Regulation of expression by promoters versus internal ribosome entry site in the 5′-untranslated sequence of the human cyclin-dependent kinase inhibitor p27 kip1, Nucleic Acids Research, Volume 33, Issue 12, 1 July 2005, Pages 3763–3771, https://doi.org/10.1093/nar/gki680en_US
dc.identifier.urihttps://hdl.handle.net/1805/24589
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.relation.isversionof10.1093/nar/gki680en_US
dc.relation.journalNucleic Acids Researchen_US
dc.rightsAttribution-NonCommercial 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.sourcePublisheren_US
dc.subjectregulateden_US
dc.subjectinternal ribosomeen_US
dc.subject50 -untranslated sequenceen_US
dc.subjectcyclin-dependent kinaseen_US
dc.titleRegulation of expression by promoters versus internal ribosome entry site in the 5′-untranslated sequence of the human cyclin-dependent kinase inhibitor p27en_US
dc.typeArticleen_US
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