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  • Original Paper
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Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein

Oncogene volume 20, pages 6152–6163 (2001)Cite this article

Abstract

Cell cycle control by pRb requires the integrity of the pocket domain, which is a region necessary for interactions with a variety of proteins, including E2F and LXCXE-motif containing proteins. Through knowledge of the crystal structure of pRb we have prepared a panel of pRb mutant derivatives in which a cluster of lysine residues that demark the LXCXE peptide binding domain were systematically mutated. One of the mutant derivatives, Rb6A, exhibits significantly reduced LXCXE-dependent interactions with HPV E7, cyclinD1 and HDAC2, but retained LXCXE-independent binding to E2F. Consistent with these results, Rb6A could down-regulate E2F-1-dependent activation of different E2F responsive promoters, but was compromised in Rb-dependent repression. Most importantly, Rb6A retained wild-type growth arrest activity, and colony forming activity similar to wild-type pRb. It is compatible with these results that directly targeting HDAC2 to E2F responsive promoters as an E2F/HDAC hybrid protein failed to effect cell cycle arrest. These results suggest that LXCXE-dependent interactions are not essential for pRb to exert growth arrest.

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Acknowledgements

We thank Marie Caldwell for help in preparing this manuscript. This work was supported by the Medical Research Council, Wellcome Trust, Leukaemia Research Fund and Cancer Research Campaign.

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  1. Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK

    Ho Man Chan, Linda Smith & Nicholas B La Thangue

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  1. Ho Man Chan
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Correspondence to Nicholas B La Thangue.

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Chan, H., Smith, L. & La Thangue, N. Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma protein. Oncogene 20, 6152–6163 (2001). https://doi.org/10.1038/sj.onc.1204793

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