Abstract |
The formation of fusion genes between NUP98 and members of the HOX family represents a critical factor for the genesis of acute leukemia or acute transformation of chronic myeloid leukemia (CML). To gain insights into the molecular mechanisms underlying the leukemogenesis of NUP98-HOX fusion products, we cloned NUP98-PMX1 from a CML- blast crisis patient with t(1;11) as a secondary chromosomal translocation, and functionally studied the fusion products in detail through various molecular and protein biochemical assays. In addition to many interesting features, we have found that the NUP98-PMX1 fusion protein exerts a repressive effect on PMX1 or serum response factor-mediated c-FOS activation, probably through the recruitment of a common corepressor histone deacetylase 1 by FG domains of the NUP98-PMX1 fusion protein. Moreover, we have provided evidence that the FG domains of NUP98-PMX1 and two other NUP98-containing fusion proteins, i.e., NUP98-HOXA9 and NUP98-HOXC11, all exhibit dual binding ability to both CREB binding protein, a coactivator, and histone deacetylase 1, a corepressor. Accordingly, we have hypothesized that this dual binding activity is shared by most, if not all, NUP98-HOX-involved fusion proteins, enabling these fusion proteins to act as both trans-activators and trans-repressors, and contributing to the genesis of acute leukemia or acute transformation of CML.
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Authors | Xue-Tao Bai, Bai-Wei Gu, Tong Yin, Chao Niu, Xiao-Dong Xi, Ji Zhang, Zhu Chen, Sai-Juan Chen |
Journal | Cancer research
(Cancer Res)
Vol. 66
Issue 9
Pg. 4584-90
(May 01 2006)
ISSN: 0008-5472 [Print] United States |
PMID | 16651408
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NUP98-PMX1 fusion protein, human
- Nuclear Pore Complex Proteins
- Oncogene Proteins, Fusion
- HDAC1 protein, human
- Histone Deacetylase 1
- Histone Deacetylases
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Topics |
- Binding Sites
- Blast Crisis
- Cell Nucleus
(genetics, metabolism)
- Cloning, Molecular
- Gene Expression Regulation, Leukemic
- Genes, fos
- Histone Deacetylase 1
- Histone Deacetylases
(metabolism)
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(genetics, metabolism, pathology)
- Male
- Middle Aged
- Nuclear Pore Complex Proteins
(genetics, metabolism)
- Oncogene Proteins, Fusion
(genetics, metabolism)
- Protein Structure, Tertiary
- Transcriptional Activation
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