SEARCH:   Advanced

Blood, 1 May 2005, Vol. 105, No. 9, pp. 3691-3698. Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2003-07-2558. This Article Full Text (PDF) All Versions of this Article: 2003-07-2558v1 105/9/3691    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, W. Articles by Lu, X. Search for Related Content PubMed PubMed Citation Articles by Zhang, W. Articles by Lu, X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 1, 2003 Accepted December 14, 2004 Posttranslational modifications of p27kip1 determine its binding specificity to different cyclins and cdks in vivo Wenqing Zhang, Daniele Bergamaschi, Boquan Jin, and Xin Lu* Ludwig Institute for Cancer Research,University College London, London, United Kingdom Department of Immunology, Fourth Military Medical University, Xi'an, China * Corresponding author; email: x.lu{at}ludwig.ucl.ac.uk. Using two dimensional gel electrophoresis (2D-gel) analysis, we show here that cell cycle entry is associated with a significant increase in p27kip1 phosphorylation in human primary B cells. A similar pattern of increase in p27kip1 phosphorylation was also seen in two fast growing tumour cell lines, Burkitt's lymphoma cell line BL40 and breast carcinoma cell line Cal51, where inactive p27kip1 is expressed at high levels. Detailed analysis revealed for the first time that different cyclins and cdks interact with distinct post-translationally modified isoforms of p27kip1 in vivo. Cyclin E but not cyclin A selectively interacts with phosphorylated p27kip1 isoforms while cyclin D1 and D2 favor unphosphorylated p27kip1 isoforms in vivo. Interestingly, cyclin D3 and cdk4 selectively interact with phosphorylated p27kip1 in BL40 cells. Among all D-type cyclin/cdk4 and cdk6 complexes, Cyclin D3/cdk4 is most active in sequestering the inhibitory activity of p27kip1 in vitro in a cyclinE/cdk2 kinase assay. This novel feature of the binding specificity of p27kip1 to cyclins and cdks in vivo is interpreted in the context of overexpression of cyclin D3 in the presence of high levels of p27kip1 in human B cell lymphomas with adverse clinical outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-W. Cui, Y.-J. Li, A. Sarkar, J. Brown, Y.-H. Tan, M. Premyslova, C. Michaud, N. Iscove, G.-J. Wang, and Y. Ben-David Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation Blood, October 1, 2007; 110(7): 2631 - 2640. [Abstract] [Full Text] [PDF] L. Hong, Y. Zhao, Y. Han, W. Guo, H. Jin, T. Qiao, Z. Che, and D. Fan Mechanisms of growth arrest by zinc ribbon domain-containing 1 in gastric cancer cells Carcinogenesis, August 1, 2007; 28(8): 1622 - 1628. [Abstract] [Full Text] [PDF] E. Susaki, K. Nakayama, and K. I. Nakayama Cyclin D2 Translocates p27 out of the Nucleus and Promotes Its Degradation at the G0-G1 Transition Mol. Cell. Biol., July 1, 2007; 27(13): 4626 - 4640. [Abstract] [Full Text] [PDF] S. Pyndiah, J. P. Lasserre, A. Menard, S. Claverol, V. Prouzet-Mauleon, F. Megraud, F. Zerbib, and M. Bonneu Two-dimensional Blue Native/SDS Gel Electrophoresis of Multiprotein Complexes from Helicobacter pylori Mol. Cell. Proteomics, February 1, 2007; 6(2): 193 - 206. [Abstract] [Full Text] [PDF] A. El Wakil, C. Francius, A. Wolff, J. Pleau-Varet, and J. Nardelli The GATA2 transcription factor negatively regulates the proliferation of neuronal progenitors Development, June 1, 2006; 133(11): 2155 - 2165. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020