Lanfear J, Fleming J, Walker M, Harrison P
Cancer Research-Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
Carcinogenesis. 1993 Mar;14(3):335-40. doi: 10.1093/carcin/14.3.335.
A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.
最近发现一种与对乙酰氨基酚解毒作用有关的56 kDa肝脏蛋白(AP56),因其与56 kDa硒结合蛋白(SP56)相似而被克隆:实际上,推导的AP56氨基酸序列与SP56仅有14个残基不同。从Balb/c小鼠黏粒基因组DNA文库中分离基因组DNA重组体表明,SP56和AP56由两个不同的基因编码。使用区分AP56和SP56 mRNA的寡核苷酸引物进行逆转录/PCR显示,SP56 mRNA在肝脏、肾脏中高表达,在肺中表达较少;而AP56 mRNA主要在肝脏中表达。两种mRNA在肝细胞系中往往下调,但在体内DEN诱导的肝肿瘤中仍保持高水平。根据这两种蛋白在介导硒的抗癌作用和解毒机制中的假定功能,对这些发现的相关性进行了评估。