Identification of RB1CC1, a novel human gene that can induce RB1 in various human cells.
Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful cancer treatment. Current knowledge about genes that contribute to MDR is limited, however, and its mechanisms remain unclear. To identify genes involved in MDR, we performed differential display analysis and isolated a novel human gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a putative 1594-amino-acid protein that contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure. Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus. In MDR variants of human osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin-induced cytotoxic stress and remained elevated for the duration of drug treatment. RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1) in cancer cell lines as well as in various normal human tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells. These data suggest that RB1CC1 may be a key regulator of RB1 gene expression.
Chano
Tokuhiro
T
Department of Basic Science for Health and Nursing, Shiga University of Medical Science, Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. chano@belle.shiga-med.ac.jp
Ikegawa
Shiro
S
Kontani
Keiichi
K
Okabe
Hidetoshi
H
Baldini
Nicola
N
Saeki
Yukikazu
Y
D000595:Amino Acid Sequence; D000071183:Autophagy-Related Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000071183:Autophagy-Related Proteins; C407704:RB1CC1 protein, human; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D004317:Doxorubicin; D011505:Protein-Tyrosine Kinases