LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.
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.
Sharp
Tyson V
TV
Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical Research, Cruciform Building, University College London, London WC1E 6BT, United Kingdom. t.sharp@ucl.ac.uk
Munoz
Fernando
F
Bourboulia
Dimitra
D
Presneau
Nadege
N
Darai
Eva
E
Wang
Hsei-Wei
HW
Cannon
Mark
M
Butcher
David N
DN
Nicholson
Andrew G
AG
Klein
George
G
Imreh
Stephan
S
Boshoff
Chris
C
D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C403807:LIMD1 protein, human; C509775:Limd1 protein, mouse; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA