Supplementary Figure 1 from An Essential Role of Alternative Splicing of c-myc Suppressor FUSE-Binding Protein–Interacting Repressor in Carcinogenesis

Matsushita, Kazuyuki; Tomonaga, Takeshi; Shimada, Hideaki; Shioya, Ayumi; Higashi, Morihiro; Matsubara, Hisahiro; Harigaya, Kenichi; Nomura, Fumio; Libutti, Daniel; Levens, David; Ochiai, Takenori

doi:10.1158/0008-5472.22366848.v1

00085472can044459-sup-supplementary_figure_1.pdf (43.54 kB)

Supplementary Figure 1 from An Essential Role of Alternative Splicing of c-myc Suppressor FUSE-Binding Protein–Interacting Repressor in Carcinogenesis

journal contribution

posted on 2023-03-30, 17:08 authored by Kazuyuki Matsushita, Takeshi Tomonaga, Hideaki Shimada, Ayumi Shioya, Morihiro Higashi, Hisahiro Matsubara, Kenichi Harigaya, Fumio Nomura, Daniel Libutti, David Levens, Takenori Ochiai

Supplementary Figure 1 from An Essential Role of Alternative Splicing of c-myc Suppressor FUSE-Binding Protein–Interacting Repressor in Carcinogenesis

History

ARTICLE ABSTRACT

Elevated expression of c-myc has been detected in a broad range of human cancers, indicating a key role for this oncogene in tumor development. Recently, an interaction between FUSE-binding protein–interacting repressor (FIR) and TFIIH/p89/XPB helicase was found to repress c-myc transcription and might be important for suppressing tumor formation. In this study, we showed that enforced expression of FIR induced apoptosis. Deletion of the NH2-terminal repression domain of FIR rescued the cells from apoptosis as did coexpression of c-Myc with FIR; thus, repression of Myc mediates FIR-driven apoptosis. Surprisingly, a splicing variant of FIR unable to repress c-myc or to drive apoptosis was frequently discovered in human primary colorectal cancers but not in the adjacent normal tissues. Coexpression of this splicing variant with repressor-competent FIR, either in HeLa cells or in the colon cancer cell line SW480, not only abrogated c-Myc suppression but also inhibited apoptosis. These results strongly suggest the expression of this splicing variant promotes tumor development by disabling FIR repression and sustaining high levels of c-Myc and opposing apoptosis in colorectal cancer. (Cancer Res 2006; 66(3): 1409-17)