Nucleolar protein P120 and its targeting for cancer chemotherapy.
Identification of the G1-P120 antigen with the aid of the monoclonal antibody to its "human-specific epitope" has resulted in rapid development of information on its molecular biology. With the monoclonal antibody, it rapidly became possible to identify and subsequently sequence its cDNA and with cDNA clones to isolate and sequence its genomic DNA. It was demonstrated that the protein had 4 major domains: a basic domain, an acidic domain, a hydrophobic and methionine-rich domain and a domain rich in cysteine and proline residues. In addition to a nuclear recognition signal, the epitope region is juxtaposed to phosphorylation sites. The epitope region contains the sequence Gln-Ala-Ala-Ala-Gly-Ile-Asn-Trp which is unique to the human P120 molecule; this may be a site for drug attack either by analogs to the region or by novel constructs based on antisense oligonucleotides. When tumor cells were transfected with antisense constructs of the P120 gene, growth rates were markedly reduced. 3T3 cells transformed by transfection with the P120 gene reverted to a nontransformed state by subsequent transfection and activation of a P120 antisense construct. Opportunities for control of malignant cells with antisense oligonucleotides are currently under study.
Busch
H
H
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Busch
R K
RK
Freeman
J W
JW
Perlaky
L
L
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001483:Base Sequence; D002453:Cell Cycle; D002466:Cell Nucleolus / Q000737:chemistry; D004247:DNA / Q000235:genetics; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology; D011496:Protein Methyltransferases; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012359:tRNA Methyltransferases
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; C065028:NOP2 protein, human; C512901:Nop2 protein, mouse; D011496:Protein Methyltransferases; D012359:tRNA Methyltransferases