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

Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16531-6. doi: 10.1073/pnas.0407123101. Epub 2004 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 3 / genetics*
  • DNA / genetics
  • DNA-Binding Proteins / metabolism
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Fibrosarcoma / genetics
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Genes, Tumor Suppressor*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retinoblastoma Protein / metabolism*
  • Subcellular Fractions / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transplantation, Heterologous
  • Tumor Stem Cell Assay
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • LIMD1 protein, human
  • Limd1 protein, mouse
  • Repressor Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • DNA