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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.

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


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
Acceptance Date Mar 7, 2011
Online Publication Date Mar 12, 2011
Publication Date Apr 6, 2011
Deposit Date Dec 6, 2018
Publicly Available Date Apr 15, 2019
Journal FEBS Letters
Print ISSN 0014-5793
Electronic ISSN 1873-3468
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 585
Issue 7
Pages 1089-1096
DOI https://doi.org/10.1016/j.febslet.2011.03.013
Public URL https://nottingham-repository.worktribe.com/output/1376955
Publisher URL https://febs.onlinelibrary.wiley.com/doi/full/10.1016/j.febslet.2011.03.013

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