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

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.

SUBMITTER: Foxler DE

PROVIDER: S-EPMC3078326 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Foxler Daniel E DE James Victoria V Shelton Samuel J SJ Vallim Thomas Q de A TQ Shaw Peter E PE Sharp Tyson V TV

FEBS letters 20110312 7

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 transcr ...[more]

PMID: 21402070

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