TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins

被引:110
作者
Yang, L
Embree, LJ
Hickstein, DD
机构
[1] Univ Washington, Sch Med, Div Oncol, Seattle, WA 98108 USA
[2] Univ Washington, Sch Med, Div Mol Med, Seattle, WA 98108 USA
[3] VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA
关键词
D O I
10.1128/MCB.20.10.3345-3354.2000
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The translocation liposarcoma (TLS) gene is fused to the ETS-related gene (ERG) in human myeloid leukemia, resulting in the generation of a TLS-ERG protein. We demonstrate that both TLS and the TLS-ERG leukemia fusion protein bind to RNA polymerase II through the TLS N-terminal domain, which is retained in the fusion protein; however, TLS recruits members of the serine-arginine (SR) family of splicing factors through its C-terminal domain, whereas the TLS-ERG fusion protein lacks the ability to recruit SR proteins due to replacement of the C-terminal domain by the fusion partner ERG. In transient-transfection assays, the TLS-ERG fusion protein inhibits E1A pre-mRNA splicing mediated by these TLS-associated SR proteins (TASR), and stable expression of the TLS-ERG fusion protein in K562 cells alters the splicing profile of CD44 mRNA. These results suggest that TLS fusion proteins may lead to cellular abnormalities by interfering with the splicing of important cellular regulators.
引用
收藏
页码:3345 / 3354
页数:10
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