Hierarchical requirement of SWI/SNF in retinoblastoma tumor suppressor-mediated repression of Plk1

Ranjaka W. Gunawardena, Hasan Siddiqui, David A. Solomon, Christopher N. Mayhew, Justin Held, Steven P. Angus, Erik S. Knudsen

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36 Scopus citations

Abstract

Plk1 (Polo-like kinase 1) is a critical regulator of cell cycle progression that harbors oncogenic activity and exhibits aberrant expression in multiple tumors. However, the mechanism through which Plk1 expression is regulated has not been extensively studied. Here we demonstrate that Plk1 is a target of the retinoblastoma tumor suppressor (RB) pathway. Activation of RB and related pocket proteins p107/p130 mediate attenuation of Plk1. Conversely, RB loss deregulates the control of Plk1 expression. RB pathway activation resulted in the repression of Plk1 promoter activity, and this action was dependent on the SWI/SNF chromatin remodeling complex. Although SWI/SNF subunits are lost during tumorigenesis and cooperate with RB for transcriptional repression, the mechanism through which SWI/SNF impinges on RB action is unresolved. Therefore, we delineated the requirement of SWI/SNF for three critical facets of Plk1 promoter regulation: transcription factor binding, corepressor binding, and histone modification. We find that E2F4 and pocket protein association with the Plk1 promoter is independent of SWI/SNF. However, these analyses revealed that SWI/SNF is required for histone deacetylation of the Plk1 promoter. The importance of SWI/SNF-dependent histone deacetylation of the Plk1 promoter was evident, because blockade of this event restored Plk1 expression in the presence of active RB. In summary, these data demonstrate that Plk1 is a target of the RB pathway. Moreover, these findings demonstrate a hierarchical role for SWI/SNF in the control of promoter activity through histone modification.

Original languageEnglish (US)
Pages (from-to)29278-29285
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
Publication statusPublished - Jul 9 2004

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Gunawardena, R. W., Siddiqui, H., Solomon, D. A., Mayhew, C. N., Held, J., Angus, S. P., & Knudsen, E. S. (2004). Hierarchical requirement of SWI/SNF in retinoblastoma tumor suppressor-mediated repression of Plk1. Journal of Biological Chemistry, 279(28), 29278-29285. https://doi.org/10.1074/jbc.M400395200