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

Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L, Lawrence JB, Penman S, Lian JB, Stein GS, Hiebert SW
Proc Natl Acad Sci U S A. 1997 94 (13): 6746-51

PMID: 9192636 · PMCID: PMC21229 · DOI:10.1073/pnas.94.13.6746

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.

MeSH Terms (14)

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

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