Citation

  • Authors: Foxler, D. E., James, V., Shelton, S. J., Vallim, T. Q., Shaw, P. E., Sharp, T. V.
  • Year: 2011
  • Journal: FEBS Lett 585 1089-96
  • Applications: in vitro / siRNA / INTERFERin
  • Cell type: U-2 OS
    Description: Human bone osteosarcoma
    Known as: U2OS

Abstract

LIMD1 is a tumour suppressor gene (TSG) down regulated in approximately 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.

Pubmed