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

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...

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Detalles Bibliográficos
Autores principales: Foxler, Daniel E., James, Victoria, Shelton, Samuel J., Vallim, Thomas Q. de A., Shaw, Peter E., Sharp, Tyson V.
Formato: Texto
Lenguaje:English
Publicado: Elsevier Science B.V 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078326/
https://www.ncbi.nlm.nih.gov/pubmed/21402070
http://dx.doi.org/10.1016/j.febslet.2011.03.013
Descripción
Sumario: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.

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