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

Congmei Zeng, Andre J van Wijnen, Janet L. Stein, Shari Meyers, Wuhua Sun, Lindsay Shopland, Jeanne B. Lawrence, Sheldon Penman, Jane B. Lian, Gary S. Stein, Scott W. Hiebert

Research output: Contribution to journalArticle

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Abstract

Transcription factors of the AML (core binding factor-α/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.

Original languageEnglish (US)
Pages (from-to)6746-6751
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number13
DOIs
StatePublished - Jun 24 1997
Externally publishedYes

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Nuclear Matrix
Leukemia
Transcription Factors
Bone and Bones
Core Binding Factors
Transcription Factor 3
Nuclear Localization Signals
Trans-Activators
Alternative Splicing
Genes
Carrier Proteins
Gene Expression
Amino Acids
DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-α transcription factors. / Zeng, Congmei; van Wijnen, Andre J; Stein, Janet L.; Meyers, Shari; Sun, Wuhua; Shopland, Lindsay; Lawrence, Jeanne B.; Penman, Sheldon; Lian, Jane B.; Stein, Gary S.; Hiebert, Scott W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 13, 24.06.1997, p. 6746-6751.

Research output: Contribution to journalArticle

Zeng, C, van Wijnen, AJ, Stein, JL, Meyers, S, Sun, W, Shopland, L, Lawrence, JB, Penman, S, Lian, JB, Stein, GS & Hiebert, SW 1997, 'Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-α transcription factors', Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 13, pp. 6746-6751. https://doi.org/10.1073/pnas.94.13.6746
Zeng, Congmei ; van Wijnen, Andre J ; Stein, Janet L. ; Meyers, Shari ; Sun, Wuhua ; Shopland, Lindsay ; Lawrence, Jeanne B. ; Penman, Sheldon ; Lian, Jane B. ; Stein, Gary S. ; Hiebert, Scott W. / Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-α transcription factors. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 13. pp. 6746-6751.
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