A novel mechanism of alternative promoter and splicing regulates the epitope generation of tumor antigen CML66-L.
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.
Yan
Yan
Y
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Phan
Leuyen
L
Yang
Fan
F
Talpaz
Moshe
M
Yang
Yu
Y
Xiong
Zeyu
Z
Ng
Bernard
B
Timchenko
Nikolai A
NA
Wu
Catherine J
CJ
Ritz
Jerome
J
Wang
Hong
H
Yang
Xiao-Feng
XF
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
D000951:Antigens, Neoplasm; D000939:Epitopes; D016898:Interferon-alpha; C431278:NUDCD1 protein, human; D020033:Protein Isoforms