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PU.1 is a major transcriptional activator of the tumour suppressor gene LIMD1

Foxler, Daniel E.; James, Victoria; Shelton, Samuel J.; de A. Vallim, Thomas Q.; Shaw, Peter E.; Sharp, Tyson V.

Authors

Daniel E. Foxler

Samuel J. Shelton

Thomas Q. de A. Vallim

Peter E. Shaw

Tyson V. Sharp



Abstract

LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG in childhood acute lymphoblastic leukaemia. Mechanistically, LIMD1 interacts with pRB, repressing E2F‐driven transcription as well as being a critical component of microRNA‐mediated gene silencing. In this study we show a CpG island within the LIMD1 promoter contains a conserved binding motif for the transcription factor PU.1. Mutation of the PU.1 consensus reduced promoter driven transcription by 90%. ChIP and EMSA analysis demonstrated that PU.1 specifically binds to the LIMD1 promoter. siRNA depletion of PU.1 significantly reduced endogenous LIMD1 expression, demonstrating that PU.1 is a major transcriptional activator of LIMD1.

Journal Article Type Article
Publication Date Apr 6, 2011
Journal FEBS Letters
Print ISSN 0014-5793
Electronic ISSN 1873-3468
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 585
Issue 7
Pages 1089-1096
APA6 Citation Foxler, D. E., James, V., Shelton, S. J., de A. Vallim, T. Q., Shaw, P. E., & Sharp, T. V. (2011). PU.1 is a major transcriptional activator of the tumour suppressor gene LIMD1. FEBS Letters, 585(7), 1089-1096. https://doi.org/10.1016/j.febslet.2011.03.013
DOI https://doi.org/10.1016/j.febslet.2011.03.013
Publisher URL https://febs.onlinelibrary.wiley.com/doi/full/10.1016/j.febslet.2011.03.013

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