Molecular characterization of a novel, cadmium-inducible gene from the nematode Caenorhabditis elegans. A new gene that contributes to the resistance to cadmium toxicity.
Cadmium is an environmental contaminant that is both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-response proteins. We previously reported the identification of 48 cadmium-inducible mRNAs in the nematode Caenorhabditis elegans. Here we describe a new cadmium-responsive gene, designated cdr-1, whose rate and level of inducible expression parallel those of the C. elegans metallothioneins. The CDR-1 mRNA contains an open reading frame of 831 bp and encodes a predicted 32-kDa, integral membrane protein. Following cadmium exposure, cdr-1 is transcribed exclusively in intestinal cells of post-embryonic C. elegans. In vivo, the CDR-1 protein is targeted specifically to the intestinal cell lysosomes. cdr-1 transcription is significantly induced by cadmium but not by other tested stressors. These results indicate that cdr-1 expression is regulated by cadmium and in a cell-specific fashion. Inhibition of CDR-1 expression renders C. elegans susceptible to cadmium toxicity. In conclusion, cdr-1 defines a new class of cadmium-inducible genes and encodes an integral membrane, lysosomal protein. This protein functions to protect against cadmium toxicity.
Liao
Vivian Hsiu-Chuan
VH
Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708, USA.
Dong
Jie
J
Freedman
Jonathan H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002104:Cadmium / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D017238:Genes, Helminth; D040342:Genetic Structures; D015801:Helminth Proteins / Q000032:analysis / Q000737:chemistry; D008969:Molecular Sequence Data; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
D018076:DNA, Complementary; D015801:Helminth Proteins; D012333:RNA, Messenger; D002104:Cadmium