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.

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.

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

• 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
• Contract Date: Apr 15, 2019