Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors
Department of Cell Biology
Medical Subject Headings
Amino Acid Sequence; Binding Sites; Bone and Bones; Core Binding Factor beta Subunit; DNA-Binding Proteins; Humans; Jurkat Cells; Leukemia; Molecular Sequence Data; Nuclear Matrix; Nuclear Proteins; Transcription Factor AP-2; Transcription Factors; Transfection
Cell Biology | Life Sciences | Medicine and Health Sciences
Transcription factors of the AML (core binding factor-alpha/polyoma enhancer binding protein 2) class are key transactivators of tissue-specific genes 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-1B 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 loss may be functionally linked to the modified interrelationships between nuclear structure and gene expression characteristic of cancer cells.
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Citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6746-51.
Proceedings of the National Academy of Sciences of the United States of America
Zeng, Congmei; Van Wijnen, Andre J.; Stein, Janet L.; Meyers, Shari; Sun, Wuhua; Shopland, Lindsay S.; Lawrence, Jeanne B.; Penman, Sheldon; Lian, Jane B.; Stein, Gary S.; and Hiebert, Scott W., "Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors" (1997). GSBS Student Publications. 720.