Open AccessLIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription
Author(s) -
Tyson V. Sharp,
F Muñoz,
Dimitra Bourboulia,
Nadège Presneau,
Eva Darai,
Hsei–Wei Wang,
Mark Can,
David N. Butcher,
Andrew G. Nicholson,
George Klein,
Stefan Imreh,
Chris Boshoff
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0407123101
Subject(s) - e2f , retinoblastoma , e2f1 , transcription (linguistics) , biology , tumor suppressor gene , transcription factor , suppressor , retinoblastoma protein , carcinogenesis , gene , cancer research , genetics , cell cycle , linguistics , philosophy
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.