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

FEBS Lett. 2011 Apr 6;585(7):1089-96. doi: 10.1016/j.febslet.2011.03.013. Epub 2011 Mar 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Consensus Sequence / genetics
  • CpG Islands / genetics
  • Gene Knockdown Techniques
  • Genes, Tumor Suppressor*
  • Hematopoiesis / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LIM Domain Proteins
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism
  • RNA, Small Interfering / genetics
  • Trans-Activators / chemistry
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation*

Substances

  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • LIMD1 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Small Interfering
  • Trans-Activators
  • proto-oncogene protein Spi-1