Cysteine auxotrophy of human leukemic lymphoblasts is associated with decreased amounts of intracellular cystathionase messenger ribonucleic acid.
A series of human lymphoblastoid cell lines derived from nonleukemic donors are known to be cysteine prototrophs (cys+), while several lymphoblastoid lines derived from leukemic donors are cysteine auxotrophs (cys-). Compared to the cys+ lines, the cysteine auxotrophic cell lines have been found to contain reduced amounts of cystathionase, the enzyme which catalyzes te conversion of cystathionine to cysteine, the terminal step in the cysteine biosynthetic pathway. We have developed a semiquantitative in vitro translation assay for the messenger ribonucleic acid (mRNA) which encodes cystathionase and have tested two pairs of cys-, cystathionase- and cys+, cystathionase+ cell lines for their intracellular content of this RNA. There is a close correlation between the cys- phenotype, reduced intracellular cystathionase content, and the intracellular content of enzyme-specific messenger RNA. Thus, the absolute cysteine requirement of the human leukemic, cys-, cystathionase- cell lines tested is likely due to an intracellular reduction in the functional messenger RNA coding for cystathionase. Among the possibilities that could amount for these phenomena are (1) a reduction in the rate of transcription of the cystathionase mRNA precursor, (2) an alteration in the nuclear and/or cytoplasmic processing of the primary transcripts, or (3) an alteration in the mRNA structure, resulting in a decreased efficiency of translation.
D000818:Animals; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000235:genetics*; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008190:Lyases / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism*; D008970:Molecular Weight; D011061:Poly A / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D012333:RNA, Messenger; D011061:Poly A; D008190:Lyases; D003542:Cystathionine gamma-Lyase; D003545:Cysteine