title: Beta(2)-microglobulin identified as an apoptosis-inducing factor and its characterization.
abstract: Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.
authors.affiliation: Department of Hematology and the Division of Molecular Hematopoiesis, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Terui
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Tomizuka
authors.forename: M
authors.initials: M
authors.lastname: Uwai
authors.forename: T
authors.initials: T
authors.lastname: Kasahara
authors.forename: N
authors.initials: N
authors.lastname: Kubota
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Mishima
authors.forename: M
authors.initials: M
authors.lastname: Douzono-Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Shimamura
authors.forename: J
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizaka
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Mano
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.forename: K
authors.initials: K
authors.lastname: Hatake
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D018922:HL-60 Cells / Q000737:chemistry; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D020298:U937 Cells / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009842:Oligopeptides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D001613:beta 2-Microglobulin; D019014:fas Receptor; C096429:L 709049