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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Foxler DE,James V,Shelton SJ,Vallim TQ,Shaw PE,Sharp TV

doi

10.1016/j.febslet.2011.03.013

subject

Has Abstract

pub_date

2011-04-06 00:00:00

pages

1089-96

issue

7

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(11)00166-9

journal_volume

585

pub_type

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