Akao Yukihiro, Yoshida Hitoshi, Matsumoto Kenji, Matsui Tsutomu, Hogetu Keita, Tanaka Nobuo, Usukura Jiro
Department of Genetic Diagnosis, Gifu International Institute of Biotechnology, Kakamigahara, Gifu 504-0838, Japan.
Genes Cells. 2003 Aug;8(8):671-6. doi: 10.1046/j.1365-2443.2003.00665.x.
The rck/p54 protein of 473 amino acids belongs to the family of DEAD-box/putative RNA helicase proteins. DEAD-box proteins have been implicated in a wide variety of cellular processes ranging from the initiation of protein synthesis and ribosome biosynthesis to premRNA splicing by means of modifying the RNA structure. Our previous data suggested that rck/p54 positively affected the translation initiation of c-myc mRNA.
The data obtained from morphological studies and surface plasmon resonance assays clearly indicated that the protein specifically bound to c-myc RNA transcripts (RNAs) and exhibited RNA unwinding activity toward c-myc RNAs in the presence of ATP in vitro. Experiments using a deletion mutant of rck/p54 retaining only its N-terminal 289 amino acids demonstrated that the deleted C-terminal 184 amino acid domain is involved in the RNA unwinding activity.
These findings strongly suggest that rck/p54 may play an important role in translation initiation by restructuring mRNAs even in the cell and contribute to carcinogenesis.
含有473个氨基酸的rck/p54蛋白属于DEAD盒/推定RNA解旋酶蛋白家族。DEAD盒蛋白参与了从蛋白质合成起始、核糖体生物合成到通过修饰RNA结构进行前体mRNA剪接等各种各样的细胞过程。我们之前的数据表明rck/p54对c-myc mRNA的翻译起始有正向影响。
形态学研究和表面等离子体共振分析获得的数据清楚地表明,该蛋白特异性结合c-myc RNA转录本(RNAs),并且在体外ATP存在的情况下对c-myc RNAs表现出RNA解旋活性。使用仅保留其N端289个氨基酸的rck/p54缺失突变体进行的实验表明,缺失的C端184个氨基酸结构域参与RNA解旋活性。
这些发现有力地表明,rck/p54即使在细胞内也可能通过重组mRNA在翻译起始中发挥重要作用,并有助于肿瘤发生。