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Cell cycle-independent upregulation of p27Kip1 by p21Waf1 in K562 cells

Oncogene volume 20, pages 6524–6530 (2001)Cite this article

Abstract

Cellular differentiation frequently involves sequential peaks in the expression of cyclin-dependent kinase inhibitors (cdki's). For example, an increase in levels of the cdki p27Kip1 follows upregulation of p21Waf1 in several cell types induced to differentiate by diverse stimuli. In this study, we have investigated whether p21Waf1 expression itself, rather than the differentiating agent, could be increasing p27Kip1 protein levels. We used an inducible p21Waf1 expression vector in a K562 leukemic cell model which we had previously shown to initiate differentiation following p21Waf1 upregulation. The current study reports that p21Waf1 upregulated p27Kip1 protein without altering p27Kip1 mRNA levels. This effect did not depend on G1-phase arrest–the increase in p27Kip1 occurred at all phases of the cell cycle. p21Waf1-expressing extracts inhibited phosphorylation of p27Kip1 on threonine-187, leading to decreased ubiquitination and decreased proteasomal destruction of p27Kip1. In K562 cells, upregulation of p27Kip1 by p21Waf1 during differentiation facilitated an ordered transition between these two cdki's, each of which may distinctly influence the differentiation process.

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Acknowledgements

We would like to thank Michael Meyer and Dr Albert Donnenberg for assistance with flow cytometry, and Dr Michele Pagano and Andrea Carrano for advice regarding nitrogen bomb usage. We also wish to thank Drs Candace Johnson, Robert Redner and Daniel Johnson for review of the manuscript. This work was supported in part by the Leukemia and Lymphoma Society of America Award 6111-99.

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Authors and Affiliations

  1. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, Pennsylvania, USA

    Richard A Steinman, Yalin Lu, Beatrice Yaroslavskiy & Christine Stehle

  2. Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, Pennsylvania, USA

    Richard A Steinman, Yalin Lu, Beatrice Yaroslavskiy & Christine Stehle

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  1. Richard A Steinman
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Correspondence to Richard A Steinman.

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Steinman, R., Lu, Y., Yaroslavskiy, B. et al. Cell cycle-independent upregulation of p27Kip1 by p21Waf1 in K562 cells. Oncogene 20, 6524–6530 (2001). https://doi.org/10.1038/sj.onc.1204800

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