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 Lettjournal_title
FEBS lettersauthors
Foxler DE,James V,Shelton SJ,Vallim TQ,Shaw PE,Sharp TVdoi
10.1016/j.febslet.2011.03.013subject
Has Abstractpub_date
2011-04-06 00:00:00pages
1089-96issue
7eissn
0014-5793issn
1873-3468pii
S0014-5793(11)00166-9journal_volume
585pub_type
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