Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha: Transcription factors

被引:214
作者
Zeng, CM
vanWijnen, AJ
Stein, JL
Meyers, S
Sun, WH
Shopland, L
Lawrence, JB
Penman, S
Lian, JB
Stein, GS
Hiebert, SW
机构
[1] UNIV MASSACHUSETTS, SCH MED, DEPT CELL BIOL, WORCESTER, MA 01655 USA
[2] UNIV MASSACHUSETTS, CTR CANC, WORCESTER, MA 01655 USA
[3] VANDERBILT UNIV, DEPT BIOCHEM, NASHVILLE, TN 37232 USA
[4] MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA
关键词
D O I
10.1073/pnas.94.13.6746
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transcription factors of the AML (core binding factor-alpha/polyoma enhancer binding protein 2) class are kev transactivators of tissue-specific gents of the hematopoietic and bone lineages. Alternative splicing of the AML-1 gene results in two major AML variants, AML-1 and AML-1B. We show here that the transcriptionally active AML-1B binds to the nuclear matrix, and the inactive AML-1 does not. The association of AML-1 IE with the nuclear matrix is independent of DNA binding and requires a nuclear matrix targeting signal (NMTS), a 31 amino acid segment near the C terminus that is distinct from nuclear localization signals. A similar NMTS is present in AML-2 and the bone-related AML-3 transcription factors. Fusion of the AML-1B NMTS to the heterologous GAL4-(1-147) protein directs GAL4 to the nuclear matrix. Thus, the NMTS is necessary and sufficient to target the transcriptionally active AML-1B to the nuclear matrix. The loss of the C-terminal domain of AML-1B is a frequent consequence of the leukemia-related t(8;21) and t(3;21) translocations. Our results suggest this lass may be functionally linked to the modified interrelationships between nuclear structure and gene expression characteristic of cancer cells.
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页码:6746 / 6751
页数:6
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