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.
Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708, USA.
Vivian Hsiu-Chuan
VH
Liao
Jie
J
Dong
Jonathan H
JH
Freedman
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