The conformational alteration of the mutated extracellular domain of Fas in an adult T cell leukemia cell line.
Fas (APO-1/CD95) is a cell surface receptor involved in apoptosis. Almost all adult T cell leukemia (ATL) cells express abundant Fas antigen and show apoptosis induced by IgM anti-Fas monoclonal antibody (mAb). We established the ATL cell line, RSO4, which was obtained from Fas-sensitive ATL cell line SO4 and showed resistance to apoptosis induced by the mAb. By sequencing analysis of Fas gene, we found the mutation with the transition of A-G at nucleotide 373 at exon 2 among the extracellular domain (ECD), resulting in substitution of arginine for histidine. The molecular modeling suggested the definitive conformational alteration around residues 52-58 among the cysteine-rich domain (CRD) 1. It was suggested that the polymerization of Fas antigen, which was the essential process for the efficient induction of apoptosis, was interfered by the alteration of CRD1, and that this portion, named the "histidine-rich region," played a critical role in Fas assembly.
Maeda
Takahiro
T
Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan. tmaeda@net.nagasaki-u.ac.jp
Nakayama
Susumu
S
Yamada
Yasuaki
Y
Sugahara
Kazuyuki
K
Isomoto
Hajime
H
Tawara
Masayuki
M
Yamasaki
Reishi
R
Onimaru
Yasuyuki
Y
Matsushita
Tetsuro
T
Ohzono
Yoshiyuki
Y
Kamihira
Shimeru
S
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D021621:Imaging, Three-Dimensional; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000737:chemistry* / Q000235:genetics
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D019014:fas Receptor