Sharp Tyson V, Munoz Fernando, Bourboulia Dimitra, Presneau Nadege, Darai Eva, Wang Hsei-Wei, Cannon Mark, Butcher David N, Nicholson Andrew G, Klein George, Imreh Stephan, Boshoff Chris
Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical Research, Cruciform Building, University College London, London WC1E 6BT, United Kingdom.
Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16531-6. doi: 10.1073/pnas.0407123101. Epub 2004 Nov 12.
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.
含LIM结构域蛋白1(LIMD1)由3号染色体p21.3区域编码,该区域在许多实体恶性肿瘤中常发生缺失。然而,LIMD1的功能尚不清楚。在此我们表明,LIMD1特异性地与视网膜母细胞瘤蛋白(pRB)相互作用,抑制E2F介导的转录,并抑制大多数具有E2F1反应元件的基因的表达。LIMD1在体外和体内均能抑制肿瘤生长,并且在所检测的大多数人类肺癌样本中表达下调。我们的数据表明,LIMD1是一种肿瘤抑制基因,其蛋白质产物在功能上与pRB相互作用,其缺失会促进肺癌发生。