Induction of a human carbonyl reductase gene located on chromosome 21.
Carbonyl reductase (EC 1.1.1.184) belongs to the group of enzymes called aldo-keto reductases. It is a NADPH-dependent cytosolic protein with specificity for many carbonyl compounds including the antitumor anthracycline antibiotics, daunorubicin and doxorubicin. Human carbonyl reductase was cloned from a breast cancer cell line (MCF-7). The cDNA clone contained 1219 base paires with an open reading frame corresponding to 277 amino acids encoding a protein of Mr 30,375. Southern analysis of genomic DNA digested with several restriction enzymes and analyzed by hybridization with a labeled cDNA probe indicated that carbonyl reductase is probably coded by a single gene and does not belong to a family of structurally similar enzymes. Southern analysis of 17 mouse/human somatic cell hybrids showed that carbonyl reductase is located on chromosome 21. Carbonyl reductase mRNA could be induced 3-4-fold in 24 h with 10 microM 2,(3)-t-butyl-4-hydroxyanisole (BHA), beta-naphthoflavone or Sudan 1.
Forrest
G L
GL
Division of Biology, Beckman Research Institute at the City of Hope, Duarte, CA 91010.
Akman
S
S
Krutzik
S
S
Paxton
R J
RJ
Sparkes
R S
RS
Doroshow
J
J
Felsted
R L
RL
Glover
C J
CJ
Mohandas
T
T
Bachur
N R
NR
D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D005796:Genes; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D004247:DNA; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse