title: A novel mechanism of alternative promoter and splicing regulates the epitope generation of tumor antigen CML66-L.
abstract: This report describes the difference in the epitope generation of two isoforms of self-tumor Ag CML66 and the regulation mechanism. We identified a new CML66 short isoform, termed CML66-S. The previously identified long CML66 is referred to as CML66-L. CML66-S shares the C terminus with CML66-L but has its unique N terminus. CML66-S is predominantly expressed in testis, but is also expressed in very low levels in tumor cells, whereas CML66-L is expressed in tumor cells and testis. Differential expression of CML66-L and CML66-S in tumor cells resulted from regulation at transcription, although alternative splicing also participated in the generation of the isoforms. In addition, Ab titers to a CML66-L peptide were significantly higher than that to CML66-S peptide in the sera from patients with tumors. Finally, the Abs to full-length CML66-L in the sera from patients with tumors were correlated with the Abs in the sera from these patients to CML66-L-38, which is a fusion protein with a CML66-L-specific N terminus. This suggests that the CML66-L isoform is mainly responsible for the epitope generation. Our studies have identified the alternative promoter in combination with alternative splicing as a novel mechanism for regulation of the epitope generation of a self-tumor Ag.
authors.affiliation: Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Leuyen
authors.initials: L
authors.lastname: Phan
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Xiong
authors.forename: Bernard
authors.initials: B
authors.lastname: Ng
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Timchenko
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wu
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
mesh_terms: D017398:Alternative Splicing / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D000939:Epitopes / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000628:therapy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D013737:Testis / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D016898:Interferon-alpha; C431278:NUDCD1 protein, human; D020033:Protein Isoforms