LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription

  • Tyson V. Sharp
  • , Fernando Munoz
  • , Dimitra Bourboulia
  • , Nadege Presneau
  • , Eva Darai
  • , Hsei Wei Wang
  • , Mark Cannon
  • , David N. Butcher
  • , Andrew G. Nicholson
  • , George Klein
  • , Stephan Imreh
  • , Chris Boshoff

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

LIM domains-containing protein 1 (LIMD1) is encoded at chromosome 3p21.3, a region commonly deleted in many solid malignancies. However, the function of LIMD1 is unknown. Here we show that LIMD1 specifically interacts with retinoblastoma protein (pRB), inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. LIMD1 blocks tumor growth in vitro and in vivo and is down-regulated in the majority of human lung cancer samples tested. Our data indicate that LIMD1 is a tumor-suppressor gene, the protein product of which functionally interacts with pRB and the loss of which promotes lung carcinogenesis.

Original languageEnglish
Pages (from-to)16531-16536
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
StatePublished - 23 Nov 2004
Externally publishedYes

Keywords

  • Lung cancer
  • Retinoblastoma

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