Published online 8 July 2005
Article |
Regulation of expression by promoters versus internal ribosome entry site in the 5'-untranslated sequence of the human cyclin-dependent kinase inhibitor p27kip1
Department of Pharmacology and Toxicology, Indiana University Cancer Center, Walther Oncology Center/Walther Cancer Institute, Indiana University School of Medicine 1044 W. Walnut Street, Indianapolis, IN 46202, USA
*To whom correspondence should be addressed. Tel: +1 317 278 4503; Fax: +1 317 274 8046; Email: jianzhan{at}iupui.edu
Received May 15, 2005. Accepted June 12, 2005.
p27kip1 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 p27kip1 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 p27kip1 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 p27kip1 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 p27kip1. The findings in this study indicate that transcriptional regulation likely plays an important role in p27kip1 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.
Present address: Zhaoqian Liu, Institute of Clinical Pharmacology, Central South University Xiangya School of Medicine, Changsha, People's Republic of China 410078
The authors wish to be known that, in their opinion, the first two authors should be regarded as joint First Authors
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
H. A. Saffran and J. R. Smiley The XIAP IRES activates 3' cistron expression by inducing production of monocistronic mRNA in the {beta}gal/CAT bicistronic reporter system RNA, November 1, 2009; 15(11): 1980 - 1985. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Cuesta, A. Martinez-Sanchez, and F. Gebauer miR-181a Regulates Cap-Dependent Translation of p27kip1 mRNA in Myeloid Cells Mol. Cell. Biol., May 15, 2009; 29(10): 2841 - 2851. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Desplanques, N. Giuliani, R. Delsignore, V. Rizzoli, R. Bataille, and S. Barille-Nion Impact of XIAP protein levels on the survival of myeloma cells Haematologica, January 1, 2009; 94(1): 87 - 93. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Audigier, J. Guiramand, L. Prado-Lourenco, C. Conte, I. G. Gonzalez-Herrera, C. Cohen-Solal, M. Recasens, and A.-C. Prats Potent activation of FGF-2 IRES-dependent mechanism of translation during brain development RNA, September 1, 2008; 14(9): 1852 - 1864. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Wei, M. Kanai, Z. Jia, X. Le, and K. Xie Kruppel-like Factor 4 Induces p27Kip1 Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells Cancer Res., June 15, 2008; 68(12): 4631 - 4639. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Araud, R. Genolet, P. Jaquier-Gubler, and J. Curran Alternatively spliced isoforms of the human elk-1 mRNA within the 5' UTR: implications for ELK-1 expression Nucleic Acids Res., July 9, 2007; 35(14): 4649 - 4663. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Jiang, J. Coleman, R. Miskimins, R. Srinivasan, and W. K. Miskimins Cap-independent translation through the p27 5'-UTR Nucleic Acids Res., July 9, 2007; 35(14): 4767 - 4778. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik Searching for IRES RNA, October 1, 2006; 12(10): 1755 - 1785. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. G. Bert, R. Grepin, M. A. Vadas, and G. J. Goodall Assessing IRES activity in the HIF-1{alpha} and other cellular 5' UTRs RNA, June 1, 2006; 12(6): 1074 - 1083. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Mokrejs, V. Vopalensky, O. Kolenaty, T. Masek, Z. Feketova, P. Sekyrova, B. Skaloudova, V. Kriz, and M. Pospisek IRESite: the database of experimentally verified IRES structures (www.iresite.org) Nucleic Acids Res., January 1, 2006; 34(suppl_1): D125 - D130. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kozak A second look at cellular mRNA sequences said to function as internal ribosome entry sites Nucleic Acids Res., November 28, 2005; 33(20): 6593 - 6602. [Abstract] [Full Text] [PDF] |
||||




