Cloning and characterization of LUN, a novel RING finger protein that is highly expressed in lung and specifically binds to a palindromic sequence

被引:25
作者
Chu, D
Kakazu, N
Gorrin-Rivas, MJ
Lu, HP
Kawata, M
Abe, T
Ueda, K
Adachi, Y [1 ]
机构
[1] Kyoto Univ, Inst Chem Res, Lab Mol Clin Chem, Kyoto 6110011, Japan
[2] Kyoto Prefectural Univ Med, Dept Hyg, Kamigyo Ku, Kyoto 6028566, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Surg & Surg Basic Sci, Sakyo Ku, Kyoto 6068507, Japan
[4] Kyoto Prefectural Univ Med, Dept Anat, Kamigyo Ku, Kyoto 6028566, Japan
关键词
D O I
10.1074/jbc.M010262200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We isolated cDNAs encoding a novel RING finger protein (LUN), the mRNAs of which were expressed at high levels in the lung. In, situ hybridization revealed that LUN mRNAs were expressed in the alveolar epithelium of the lung. The LUN gene locus was assigned to chromosome 9p21, which contains candidate tumor suppressor genes associated with loss of heterozygosity in more than 86% of small cell lung cancers. We clarified that LUN is localized to the nucleus and reveals Zn2+-dependent DNA binding activity. The region from amino acids 51 to 374 of LUN is responsible for DNA binding. Furthermore, we identified a novel palindromic binding consensus (5'-TCCCAGCACTTTGGGA-3') for the LUN binding. Interestingly, this LUN binding palindromic sequence is found in the upstream transcriptional regulatory region of the E-cadherin gene and two intervening regions of the talin gene. Our results suggested that LUN might be an important trans-acting transcriptional regulator for lung cancer-associated genes including E-cadherin and talin genes.
引用
收藏
页码:14004 / 14013
页数:10
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