The daunorubicin-binding protein of Mr 54,000 is an aldehyde dehydrogenase and is down-regulated in mouse liver tumors and in tumor cell lines.
A rabbit antiserum developed against purified rat liver daunorubicin-binding protein of M(r) 54,000 (DNR-BP54) cross-reacted with a mouse protein of the same molecular weight. This protein was expressed in the liver and several other organs of mice. A series of tumors and cell lines tested for the presence of the protein were negative. By immunocytochemistry, we found that DNR-BP54 was abundantly expressed in the cytoplasm of normal hepatocytes but was expressed at much lower levels in urethane-induced mouse liver tumors. By immunoscreening of a mouse liver cDNA library, we cloned the cDNA coding for DNR-BP54 and we found that this protein is aldehyde dehydrogenase-2 (EC 1.2.1.3). This result was confirmed by the dehydrogenase activity found in pure preparations of DNR-BP54 from normal rat and mouse livers, assayed with acetaldehyde as substrate and NAD as cofactor. The enzyme activity was inhibited by daunorubicin. The inhibition was found to be competitive with respect to NAD.
Division of Experimental Oncology B, Istituto Nazionale Tumori, Milano, Italy.
P
P
Banfi
C
C
Lanzi
F S
FS
Falvella
M
M
Gariboldi
R A
RA
Gambetta
T A
TA
Dragani
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D003630:Daunorubicin / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D051381:Rats; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; C484010:DNR-BP54 protein, mouse; C039213:daunorubicin-binding protein, rat; D000444:Aldehyde Dehydrogenase; D003630:Daunorubicin